GFM2 Antibody

What is GFM2 and why is it important in mitochondrial research?

GFM2 (G-Elongation Factor, Mitochondrial 2) is a mitochondrial GTPase that plays a critical role in protein synthesis by mediating the disassembly of ribosomes from messenger RNA at the termination of mitochondrial translation. It functions in collaboration with MRRF (Mitochondrial Ribosome Recycling Factor) to promote ribosome recycling through dissolution of intersubunit contacts . GFM2 is essential for maintaining proper mitochondrial function, as it ensures efficient translation termination and ribosome recycling.

The importance of GFM2 in research stems from its association with mitochondrial diseases. Mutations in the GFM2 gene have been linked to Combined Oxidative Phosphorylation Deficiency 39 and early-onset neurological presentations of mitochondrial disease . Since mitochondrial translation is crucial for maintaining mitochondrial function, disruptions in this system lead to breakdowns in the respiratory chain oxidative phosphorylation system and impaired maintenance of mitochondrial DNA . Therefore, studying GFM2 provides insights into mitochondrial translation mechanisms and related diseases.

How do I choose the most appropriate GFM2 antibody for my research?

When selecting a GFM2 antibody, consider these methodological criteria:

• Experimental application: Determine which applications (WB, IHC, IF, ELISA) you need the antibody for. Different antibodies are validated for different applications. For example, some antibodies like those from Abbexa are validated for ELISA, WB, and IF/ICC , while others may have broader application ranges.

• Species reactivity: Verify that the antibody reacts with your species of interest. Available GFM2 antibodies have varying species reactivity profiles:

  • Human only

  • Human and mouse

  • Human, mouse, and rat

• Epitope recognition: Consider which region of GFM2 the antibody recognizes. Some antibodies target:

  • Internal regions of human GFM2

  • C-terminal regions (amino acids 500 to C-terminus)

  • Specific peptide sequences

• Validation data: Review available validation data such as Western blot images, immunohistochemistry results, or immunofluorescence images provided by manufacturers .

What validation methods should I use to confirm GFM2 antibody specificity?

Comprehensive validation of GFM2 antibodies should employ multiple approaches:

• Knockout/knockdown controls: The gold standard for antibody validation is testing in GFM2 knockout or knockdown models. This approach was used in a study that examined novel GFM2 variants, where researchers assessed the steady-state levels of mitochondrial proteins in patient fibroblasts and muscle compared to controls . The absence or reduction of the GFM2 band in knockout/knockdown samples confirms specificity.

• Western blot analysis: Verify the antibody detects a band of the expected molecular weight (approximately 87 kDa for GFM2) . Check for:

  • Single, clean band at expected size

  • Absence of non-specific bands

  • Appropriate signal intensity at recommended dilutions

• Immunohistochemistry with appropriate controls:

  • Use tissues known to express GFM2 (e.g., colon cancer, kidney)

  • Include negative controls (primary antibody omission)

  • Compare staining patterns with established localization data for mitochondrial proteins

• Cross-validation with multiple antibodies: Use different antibodies targeting distinct epitopes of GFM2 to confirm consistent staining patterns and expression levels.

• Independent validation techniques: Complement antibody-based detection with non-antibody methods such as mass spectrometry or RNA expression analysis to confirm protein expression patterns.

A standardized experimental protocol based on comparing results in knockout cell lines against their isogenic parental controls, similar to the approach described for TGM2 antibodies , would provide robust validation for GFM2 antibodies.

What are the optimal conditions for Western blot detection of GFM2?

For optimal Western blot detection of GFM2, follow these methodological guidelines:

• Sample preparation:

  • For cell lysates: Prepare from relevant cell lines such as LOVO, RAW264.7, or A549 cells

  • For tissue samples: Human or mouse tissues with known GFM2 expression

  • Use RIPA or NP-40 buffer with protease inhibitors

  • Include phosphatase inhibitors if phosphorylation status is relevant

• Protein loading and separation:

  • Load 20-30 μg of total protein per lane

  • Use 8-10% SDS-PAGE gels to properly resolve the 87 kDa GFM2 protein

  • Include molecular weight markers spanning 50-100 kDa range

• Transfer conditions:

  • Transfer to PVDF membrane (preferred over nitrocellulose for higher molecular weight proteins)

  • Use wet transfer for 90 minutes at 100V or overnight at 30V at 4°C

• Blocking and antibody incubation:

  • Block with 5% non-fat dry milk or BSA in TBST for 1 hour at room temperature

  • Primary antibody dilutions:

    • For Abbexa antibodies: 1/500-1/3000 or 1/500-1/2000

    • For VWR/Bioss antibodies: 1:100-1000

    • Incubate overnight at 4°C

  • Secondary antibody recommendations:

    • Goat Anti-Rabbit IgG H&L Antibody conjugated with HRP

    • Dilution typically 1:5000-1:10000

    • Incubate for 1 hour at room temperature

• Detection and analysis:

  • Use ECL or similar chemiluminescent detection system

  • Expected GFM2 band: approximately 87 kDa

  • Verify specificity by comparing with knockout/knockdown controls

When investigating OXPHOS defects related to GFM2 dysfunction, consider analyzing multiple OXPHOS complex subunits simultaneously, as GFM2 variants have been shown to affect steady-state levels of complex I, III, and IV components in fibroblasts and muscle tissue .

How can I optimize immunofluorescence protocols for GFM2 detection?

For successful immunofluorescence detection of GFM2 in cellular contexts:

• Cell preparation:

  • Culture appropriate cell lines (e.g., A549 cells)

  • Seed cells on glass coverslips at 60-70% confluency

  • Fix with 4% paraformaldehyde (10 minutes at room temperature)

  • Permeabilize with 0.2% Triton X-100 in PBS (10 minutes)

• Blocking and antibody incubation:

  • Block with 1-5% BSA in PBS for 30-60 minutes

  • Primary antibody dilutions:

    • Abbexa antibody: 1/100-1/500

    • VWR/Bioss antibody: 1:50-200

    • Incubate overnight at 4°C or 1-2 hours at room temperature

  • Secondary antibody (fluorophore-conjugated anti-rabbit):

    • Typically use 1:500-1:1000 dilution

    • Incubate for 1 hour at room temperature in the dark

• Counterstaining and mounting:

  • Counterstain with DAPI (1:1000) for nuclear visualization

  • For mitochondrial co-localization, consider using MitoTracker or antibodies against mitochondrial markers

  • Mount with anti-fade mounting medium

• Imaging and analysis:

  • Use confocal microscopy for optimal resolution of mitochondrial structures

  • Capture z-stacks to ensure complete visualization of mitochondrial networks

  • Analyze co-localization with mitochondrial markers to confirm specificity

• Controls and validation:

  • Include secondary-only controls to assess background

  • Use siRNA knockdown cells as negative controls

  • Consider co-staining with other mitochondrial translation factors to assess functional relationships

Based on validation data, GFM2 should show punctate cytoplasmic staining consistent with mitochondrial localization. The immunofluorescence analysis of A549 cells using GFM2 antibody (#34668) demonstrated this pattern .

What considerations are important for immunohistochemical detection of GFM2 in tissue samples?

For effective immunohistochemical detection of GFM2 in tissue sections:

• Tissue preparation and processing:

  • Use formalin-fixed, paraffin-embedded (FFPE) tissue sections (4-6 μm thickness)

  • Include tissues with known GFM2 expression (e.g., colon cancer, kidney)

  • Perform antigen retrieval using citrate buffer (pH 6.0) or EDTA buffer (pH 9.0)

  • Quench endogenous peroxidase activity with 3% H₂O₂

• Antibody selection and dilution:

  • For Abcam antibody (ab230405): use 1/100 dilution

  • For Novus Biologicals: use 1:20-1:50 dilution

  • For VWR/Bioss: use 1:100-500 dilution

  • Incubate at 4°C overnight or at room temperature for 1-2 hours

• Detection system:

  • Use biotin-streptavidin HRP or polymer-based detection systems

  • Develop with DAB (3,3'-diaminobenzidine) substrate

  • Counterstain with hematoxylin for nuclear visualization

• Evaluation and scoring:

  • Assess staining intensity (0-3+)

  • Determine percentage of positive cells

  • Document subcellular localization (should be primarily cytoplasmic with granular/punctate pattern consistent with mitochondria)

• Controls and validation:

  • Include positive control tissues (colon cancer, kidney)

  • Use isotype control antibodies as negative controls

  • Consider dual staining with mitochondrial markers to confirm localization

When analyzing tissues from patients with suspected mitochondrial disorders, compare GFM2 expression patterns with those of other mitochondrial translation factors and OXPHOS components to assess potential defects in the mitochondrial translation machinery.

How do I troubleshoot weak or absent GFM2 signal in Western blots?

When facing weak or absent GFM2 signal in Western blots, systematically address these potential issues:

• Protein extraction efficiency:

  • Ensure complete lysis of mitochondria using appropriate buffers (e.g., RIPA with 1% SDS)

  • Consider mitochondrial isolation before protein extraction for enrichment

  • Verify protein concentration using reliable methods (BCA or Bradford assay)

• Antibody-specific factors:

  • Try different GFM2 antibodies targeting various epitopes

  • Adjust antibody concentration (try higher concentrations within recommended ranges)

  • Extend primary antibody incubation time (overnight at 4°C)

  • Verify antibody storage conditions (aliquot and store at -20°C, avoid freeze-thaw cycles)

• Detection system optimization:

  • Use more sensitive ECL substrates

  • Increase exposure time

  • Try different secondary antibodies with higher sensitivity

  • Consider signal amplification systems

• Technical considerations:

  • Reduce washing stringency

  • Optimize blocking conditions (try different blocking agents)

  • Ensure transfer efficiency (check with reversible stain)

  • Verify gel percentage is appropriate for 87 kDa protein

• Biological considerations:

  • Confirm GFM2 expression in your cell/tissue type

  • Consider that certain mutations or conditions might affect antibody epitope

  • Note that fibroblasts from some patients with GFM2 mutations may show normal levels of OXPHOS components despite muscle showing clear decreases

What are the best approaches for studying GFM2 dysfunction in mitochondrial disease models?

To effectively study GFM2 dysfunction in mitochondrial disease models, consider these methodological approaches:

• Patient-derived cell models:

  • Establish fibroblast cultures from patients with GFM2 mutations

  • Generate induced pluripotent stem cells (iPSCs) and differentiate into affected cell types (neurons, muscle)

  • Create isogenic controls using CRISPR/Cas9 correction of mutations

• Functional assessment of mitochondrial translation:

  • Measure mitochondrial protein synthesis using 35S-methionine pulse-labeling

  • Assess steady-state levels of mitochondrially-encoded proteins by Western blot

  • Examine mitoribosome assembly using sucrose gradient fractionation

  • Analyze GFM2-mitoribosome interactions using co-immunoprecipitation

• OXPHOS function evaluation:

  • Measure respiratory chain complex activities using spectrophotometric assays

  • Assess oxygen consumption rate (OCR) using Seahorse XF analyzers

  • Analyze ATP production capacity

  • Monitor mitochondrial membrane potential using fluorescent probes

• GFM2 variant characterization:

  • Express recombinant wild-type and mutant GFM2 proteins

  • Assess GTPase activity using purified proteins

  • Measure ribosome recycling activity in reconstituted systems

  • Perform structural studies to understand mutation impacts

• In vivo modeling:

  • Generate GFM2 knockout or knock-in mice

  • Create tissue-specific conditional knockouts to study tissue-specific effects

  • Assess developmental consequences and tissue-specific manifestations

Based on previous studies, focus on analyzing specific OXPHOS defects, as GFM2 variants have been associated with decreased steady-state levels of complex I (NDUFB8), complex III (CYTB, CORE2), and complex IV (COXI, COXII) components in patient-derived fibroblasts and muscle tissue .

How can I analyze the interaction between GFM2 and MRRF in mitochondrial ribosome recycling?

To investigate the functional interaction between GFM2 and MRRF in mitochondrial ribosome recycling:

• Co-immunoprecipitation (Co-IP) studies:

  • Use anti-GFM2 antibodies to pull down protein complexes

  • Probe Western blots with anti-MRRF antibodies

  • Perform reciprocal Co-IP with anti-MRRF antibodies

  • Include RNase treatment to determine RNA-dependence of interactions

• Proximity ligation assay (PLA):

  • Visualize GFM2-MRRF interactions in situ

  • Use specific antibodies against GFM2 and MRRF

  • Quantify interaction signals in different cellular conditions

  • Compare wild-type vs. disease-associated variants

• Bimolecular fluorescence complementation (BiFC):

  • Tag GFM2 and MRRF with complementary fragments of fluorescent proteins

  • Analyze reconstitution of fluorescence as indication of interaction

  • Perform live-cell imaging to study dynamics of interaction

• In vitro ribosome recycling assays:

  • Purify recombinant GFM2 and MRRF proteins

  • Isolate mitochondrial ribosomes

  • Measure GTP hydrolysis during ribosome recycling

  • Assess ribosome disassembly using light scattering or sedimentation analysis

• Structure-function analysis:

  • Generate domain deletion mutants of GFM2

  • Assess which regions are critical for MRRF interaction

  • Examine how disease-associated mutations affect interaction

  • Use cryo-EM to visualize GFM2-MRRF-ribosome complexes

Since research has established that GFM2 promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts and acts in collaboration with MRRF , these methodologies will help elucidate the molecular mechanisms and regulatory factors involved in this essential process.

How can GFM2 antibodies be used to study mitochondrial dysfunction in neurological disorders?

GFM2 antibodies offer valuable tools for investigating mitochondrial dysfunction in neurological disorders through these methodological approaches:

• Tissue-based analyses:

  • Perform immunohistochemistry on brain tissue from patients with neurological disorders

  • Compare GFM2 expression patterns in affected vs. unaffected regions

  • Analyze co-expression with other mitochondrial markers

  • Assess correlations between GFM2 expression and markers of neurodegeneration

• Patient-derived models:

  • Establish fibroblast cultures from patients with early-onset neurological presentations

  • Generate neural cells through direct conversion or iPSC differentiation

  • Compare GFM2 expression and localization between patient and control neural cells

  • Assess impact of GFM2 variants on neural development and function

• Mitochondrial translation assessment:

  • Analyze steady-state levels of mitochondrially-encoded proteins in neural tissues

  • Assess correlation between GFM2 dysfunction and OXPHOS defects in neurons

  • Examine region-specific variations in mitochondrial translation efficiency

• Biomarker development:

  • Evaluate GFM2 expression changes in accessible patient samples (blood, CSF)

  • Determine if GFM2 antibodies can detect circulating mitochondrial components released during neuronal damage

  • Correlate GFM2-related markers with disease progression

• Therapeutic monitoring:

  • Use GFM2 antibodies to assess mitochondrial responses to therapeutic interventions

  • Monitor restoration of mitochondrial translation in treated patients

  • Develop companion diagnostics for therapies targeting mitochondrial function

Research has established links between GFM2 variants and early-onset neurological presentations of mitochondrial disease . Patients presented with global developmental delay, raised CSF lactate, and abnormalities on cranial MRI. GFM2 antibodies can help monitor mitochondrial dysfunction in these conditions and potentially identify similar mechanisms in other neurological disorders.

What is the significance of GFM2 expression analysis in mitochondrial disease diagnosis?

GFM2 expression analysis using antibody-based techniques provides valuable diagnostic and research insights for mitochondrial diseases:

• Diagnostic applications:

  • Immunohistochemical analysis of muscle biopsies from suspected mitochondrial disease patients

  • Western blot assessment of GFM2 protein levels in patient-derived fibroblasts

  • Correlation of GFM2 expression with respiratory chain deficiencies

  • Distinguishing GFM2-related disorders from other mitochondrial translation defects

• Interpretation of genetic findings:

  • Functional validation of GFM2 variants identified through genetic testing

  • Assessment of protein expression in carriers of GFM2 variants

  • Determination of pathogenicity for variants of uncertain significance (VUS)

  • Correlation of genotype with protein expression patterns

• Tissue-specific manifestations:

  • Comparison of GFM2 expression across affected tissues

  • Analysis of why certain mutations affect specific tissues (e.g., brain vs. muscle)

  • Detection of tissue-specific isoforms or post-translational modifications

• Clinical correlations:

  • Relationship between GFM2 protein levels and disease severity

  • Longitudinal monitoring of GFM2 expression during disease progression

  • Correlation with biochemical markers (lactate, pyruvate, amino acids)

• Research applications:

  • Development of biomarkers for mitochondrial translation defects

  • Screening compounds that may restore GFM2 expression or function

  • Understanding compensatory mechanisms in different tissues

Previous studies have demonstrated that mutations in GFM2 can result in combined oxidative phosphorylation deficiency 39 and are associated with early-onset neurological presentations of mitochondrial disease . GFM2 antibodies were crucial in these studies for confirming loss of protein expression and associated OXPHOS subunit defects in patient muscles, providing important diagnostic confirmation of the genetic findings.

How can GFM2 antibodies be used to monitor therapeutic responses in mitochondrial translation disorders?

GFM2 antibodies offer valuable tools for monitoring therapeutic interventions targeting mitochondrial translation disorders:

• Baseline assessment:

  • Quantify GFM2 protein expression in patient samples before intervention

  • Determine pattern and severity of associated OXPHOS defects

  • Establish correlation between GFM2 levels and clinical/biochemical parameters

• Therapeutic monitoring strategies:

  • Serial analysis of GFM2 expression in accessible tissues (blood, skin fibroblasts)

  • Assessment of OXPHOS subunit recovery following therapy

  • Correlation of GFM2/OXPHOS normalization with clinical improvement

  • Monitoring of mitochondrial biogenesis markers alongside GFM2

• Cell-based therapeutic screening:

  • Evaluate candidate compounds in patient-derived cells using GFM2 antibodies

  • Identify molecules that stabilize mutant GFM2 or upregulate compensatory pathways

  • Screen for compounds that bypass GFM2 defects by alternative ribosome recycling mechanisms

• Gene therapy assessment:

  • Monitor GFM2 expression following gene replacement therapy

  • Assess restoration of mitochondrial translation using pulse-labeling

  • Evaluate localization and function of introduced wild-type GFM2

• Personalized medicine applications:

  • Use GFM2 antibodies to classify patients into subgroups based on residual protein expression

  • Guide therapy selection based on specific molecular defects

  • Predict responsiveness to specific interventions based on GFM2 variant type

A methodological approach would include collecting baseline and follow-up samples from multiple tissues when possible, with standardized protocols for protein extraction and antibody-based detection. Quantification should use internal standards and normalization to housekeeping proteins to ensure comparability across time points and between patients.

How do post-translational modifications affect GFM2 function and antibody recognition?

Post-translational modifications (PTMs) of GFM2 can significantly impact both protein function and antibody recognition:

• Known and predicted PTMs of GFM2:

  • Phosphorylation at serine/threonine residues may regulate GTPase activity

  • Acetylation could affect protein stability or interaction with mitochondrial ribosomes

  • Ubiquitination may regulate protein turnover

  • N-terminal processing of mitochondrial targeting sequence occurs upon import

• Impact on antibody recognition:

  • Epitope masking: PTMs within antibody epitopes may prevent binding

  • Conformational changes: PTMs distant from epitopes may alter protein folding

  • Protocol considerations: Phosphatase treatment before immunoblotting may alter detection

  • Selection strategy: Choose antibodies targeting regions less likely to be modified

• Methodological approaches to study PTM effects:

  • Use phospho-specific antibodies if key regulatory phosphorylation sites are identified

  • Compare detection with multiple antibodies targeting different GFM2 regions

  • Perform 2D gel electrophoresis to separate GFM2 isoforms before immunoblotting

  • Use mass spectrometry to identify PTMs in immunoprecipitated GFM2

• Functional significance:

  • GTPase activity assays with modified vs. unmodified GFM2

  • Ribosome binding studies to assess impact on interaction

  • Cellular localization changes in response to stress or signaling events

  • Cell-cycle dependent modifications affecting mitochondrial translation

• Research considerations:

  • Include phosphatase inhibitors during protein extraction if studying phosphorylation

  • Consider comparing PTM patterns between normal and disease states

  • Assess PTM changes in response to mitochondrial stress

When selecting GFM2 antibodies for studies involving PTMs, consider epitope location relative to known or predicted modification sites, and validate detection specificity under conditions that may alter the PTM status of the protein.

What approaches can be used to study GFM2 interactions with the mitochondrial ribosome?

To investigate GFM2 interactions with the mitochondrial ribosome, employ these methodological approaches:

• Co-immunoprecipitation and pulldown assays:

  • Use GFM2 antibodies to immunoprecipitate native complexes

  • Analyze co-precipitated mitoribosomal proteins by Western blot or mass spectrometry

  • Perform reciprocal IP with antibodies against mitoribosomal proteins

  • Include GTP/GDP and non-hydrolyzable GTP analogs to capture different interaction states

• Proximity-based interaction mapping:

  • BioID or APEX2 proximity labeling with GFM2 as the bait

  • Crosslinking mass spectrometry (XL-MS) to identify interaction interfaces

  • FRET or BRET analysis with fluorescently tagged GFM2 and ribosomal proteins

  • Proximity ligation assay (PLA) for in situ visualization of interactions

• Structural approaches:

  • Cryo-electron microscopy of GFM2-ribosome complexes

  • Hydrogen-deuterium exchange mass spectrometry to map interaction surfaces

  • Molecular docking based on available structural information

  • Cryogenic electron tomography of mitochondria to visualize native complexes

• Functional interaction assays:

  • GTP hydrolysis assays in the presence/absence of ribosomes

  • Ribosome recycling assays with purified components

  • mRNA release assays to assess functional outcomes

  • Toeprinting assays to monitor ribosome position on mRNA

• Mutational analysis:

  • Structure-guided mutagenesis of GFM2 to identify key residues for interaction

  • Assessment of disease-associated mutations on ribosome binding

  • Domain deletion analysis to map interaction regions

  • Chimeric protein analysis with related factors (GFM1/EFG1)

Research has established that GFM2 promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts , and GTP hydrolysis likely occurs on the ribosome large subunit . These approaches will help elucidate the molecular details of these interactions and how they are affected in disease states.

How do GFM2 antibodies compare with antibodies against other mitochondrial translation factors?

A comparative analysis of GFM2 antibodies with those against other mitochondrial translation factors reveals important methodological considerations:

• Specificity and cross-reactivity:

  • GFM2 antibodies must distinguish between GFM2 and the closely related GFM1/EFG1

  • Sequence homology between mitochondrial translation factors requires careful epitope selection

  • Validation in knockout/knockdown systems is particularly important

  • Cross-reactivity testing against related family members should be performed

• Detection challenges comparison:

  Factor	MW (kDa)	Typical Expression Level	Common Detection Issues
  GFM2	87	Moderate	Background bands, variable expression
  GFM1/EFG1	83	Moderate to high	Cross-reactivity with GFM2
  TUFM	49	High	Generally reliable detection
  MRRF	29	Low	Sensitivity issues in some tissues
  MTRF1/RF1	39	Low	Background bands, sensitivity

• Application performance:

  • Western blot: GFM2 antibodies generally perform similarly to other translation factor antibodies, with expected band at 87 kDa

  • Immunohistochemistry: GFM2 antibodies show mitochondrial staining patterns comparable to other translation factors

  • Immunoprecipitation: Variable efficiency depending on epitope accessibility

  • Flow cytometry: Limited data compared to other mitochondrial markers

• Validation approaches:

  • Genetic models: Knockout validation similar to other factors

  • Disease samples: GFM2 antibodies can detect protein depletion in patient samples with GFM2 mutations

  • Multi-antibody validation: Using multiple antibodies against different epitopes is recommended for all translation factors

• Research context differences:

  • GFM2 studies often focus on ribosome recycling mechanisms

  • GFM1/EFG1 research emphasizes elongation steps of translation

  • Combined analyses of multiple factors provide comprehensive insights into mitochondrial translation

When designing experiments examining mitochondrial translation, consider parallel analysis of multiple factors (GFM2, GFM1, TUFM, MRRF) to gain comprehensive insights into the process and potential compensatory mechanisms.

What can we learn from comparing GFM2 expression across different tissues and disease states?

Comparative analysis of GFM2 expression across tissues and disease states provides valuable insights into mitochondrial translation regulation:

• Tissue-specific expression patterns:

  • Analyze GFM2 protein levels across tissues using Western blot and IHC

  • Compare expression ratios of GFM2 to other translation factors

  • Correlate with tissue-specific mitochondrial content and activity

  • Investigate tissue-specific isoforms or post-translational modifications

• Methodological approach for comprehensive comparison:

  • Standardized protein extraction protocols across tissues

  • Normalization to both total protein and mitochondrial markers

  • Multi-antibody approach targeting different GFM2 epitopes

  • Correlation with functional measures of mitochondrial translation

• Disease state comparisons:

  • GFM2-specific pathologies: Analyze protein expression in patients with GFM2 mutations

  • Other mitochondrial diseases: Compare GFM2 expression in various mitochondrial disorders

  • Non-mitochondrial diseases with secondary mitochondrial dysfunction

  • Aging-related changes in GFM2 expression

• Correlation with OXPHOS defects:

  • Patient studies show tissue-specific OXPHOS consequences of GFM2 deficiency

  • Fibroblasts may show normal OXPHOS despite muscle showing clear defects

  • Different tissues show varied complex deficiencies (complex I, III, IV)

  • Pattern analysis may help predict affected tissues in individual patients

• Research and diagnostic applications:

  • Tissue-specific biomarker development based on GFM2 expression

  • Prediction of tissue vulnerability to mitochondrial translation defects

  • Potential compensatory mechanisms in unaffected tissues

  • Therapeutic targeting strategies based on tissue-specific regulation