TIMMDC1 (Translocase of Inner Mitochondrial Membrane Domain-Containing protein 1) is a 32 kDa, multi-pass membrane protein localized to the mitochondrial inner membrane. It functions as an assembly factor for mitochondrial complex I, the largest enzyme in the electron transport chain (ETC) . TIMMDC1 interacts with the MCIA complex (mitochondrial complex I assembly factor complex) and stabilizes core complex I subunits, including those encoded by mitochondrial DNA . Its depletion disrupts complex I activity, leading to impaired mitochondrial respiration and ATP production .
Several TIMMDC1 antibodies are available, differing in host species, clonality, and validated applications:
| Antibody Source | Host/Clonality | Applications | Immunogen | Reactivity |
|---|---|---|---|---|
| Abcam (ab171978) | Rabbit/Monoclonal | IP, WB, ICC/IF | Full-length TIMMDC1 | Human |
| Proteintech (23622-1-AP) | Rabbit/Polyclonal | WB, ELISA | Recombinant TIMMDC1 fusion protein | Human |
| Antibodies-Online (ABIN7270929) | Rabbit/Polyclonal | WB, IHC | AA 206–285 of human TIMMDC1 | Human, Mouse, Rat |
These antibodies are used in Western blot (WB) to detect TIMMDC1 protein levels, immunoprecipitation (IP) to study protein interactions, and immunofluorescence (ICC/IF) to localize TIMMDC1 within mitochondria .
TIMMDC1 Deficiency: A deep intronic variant (c.597-1340A>G) causes aberrant splicing and nonsense-mediated decay of TIMMDC1 mRNA, leading to undetectable protein levels in patient cells . Western blot using Abcam’s ab171978 confirmed this deficiency in a consanguineous family with mitochondrial complex I dysfunction .
Complex I Biogenesis: Proteomic studies with TIMMDC1 knockdown revealed reduced stability of complex I subunits, underscoring its role in assembly .
Gastric Cancer: Knockdown of TIMMDC1 in SGC-7901 and BGC-823 cells (validated via WB with Proteintech’s 23622-1-AP) inhibited tumor growth and metastasis by impairing complex I activity, glycolysis, and AKT/GSK3β/β-catenin signaling .
Ovarian Cancer: miR-450a regulates TIMMDC1 expression to suppress tumor growth by modulating energy metabolism .
Methodology: Western blot with Abcam’s ab171978 detected undetectable TIMMDC1 in patient fibroblasts .
Outcome: Confirmed TIMMDC1 deficiency as the cause of complex I dysfunction in two siblings with early-onset epilepsy and neuropathy .
Methodology: TIMMDC1 knockdown in SGC-7901 cells (validated via qRT-PCR and WB with Proteintech’s 23622-1-AP) reduced tumor volume by 78% in xenograft models .
Outcome: Highlighted TIMMDC1 as a potential therapeutic target for gastric cancer .
Specificity: Cross-reactivity with homologous proteins must be ruled out. For example, Antibodies-Online’s ABIN7270929 cross-reacts with mouse and rat TIMMDC1 .
Validation: Western blot optimization (e.g., 1:500–1:2000 dilution for Proteintech’s 23622-1-AP) and positive controls (e.g., HepG2 lysate) are critical .
Mitochondrial Context: TIMMDC1 antibodies must be used alongside markers for complex I subunits (e.g., NDUFAF1) to confirm assembly defects .