Mitochondrial import receptor subunit TOM40 homolog

TOMM40 (mitochondrial import receptor subunit TOM40 homolog) is a channel-forming protein that comprises part of the translocase of the outer mitochondrial membrane (TOM) complex, essential for recognition and translocation of cytosolically synthesized preproteins into mitochondria (UniProt: O96008). It stabilizes PINK1 kinase at depolarized mitochondria to promote mitophagy and assists in assembly of the respiratory chain NADH dehydrogenase complex by mediating cytosolic-to-mitochondrial translocation of Complex I components.

The protein localizes to the mitochondrial outer membrane and functions within the broader context of mitochondrial bioenergetics and quality control pathways (UniProt: O96008). TOMM40 interacts with ion channel VDAC2 and the E3 ubiquitin ligase PRKN to coordinate mitochondrial health surveillance.

TOMM40 is downregulated in Alzheimer's Disease brain tissue relative to age-matched controls (mean log2 fold-change: −0.77, Chaparral AD proteomics). This reduction was observed across post-mortem human brain subcellular fractions in TMT-labeled mass spectrometry analysis, suggesting impaired mitochondrial protein import capacity and potentially compromised mitochondrial integrity in AD pathology.