MICOS complex subunit MIC25

CHCHD6 (MICOS complex subunit MIC25) is a 235-amino-acid protein that functions as a component of the MICOS (mitochondrial contact site and cristae organizing system) complex. This large protein assembly resides in the mitochondrial inner membrane and is essential for maintaining crista junctions, organizing inner membrane architecture, and establishing contact sites between inner and outer membranes (UniProt: Q9BRQ6).

The MICOS complex plays a fundamental role in mitochondrial structure and function, with implications for cellular energy metabolism and stress responses. CHCHD6 localizes to mitochondrial subcellular fractions, where it contributes to the structural integrity required for optimal mitochondrial performance.

In Alzheimer's disease, CHCHD6 is significantly downregulated in post-mortem brain tissue from AD patients compared to age-matched controls (mean log2 fold-change −0.567; Chaparral AD proteomics). This reduction was detected across a subcellular proteomics study using tandem mass tag labeling and data-dependent acquisition analysis of four fractions (P2, P3, S2, S3). The downregulation of a critical mitochondrial structural protein suggests potential mitochondrial dysfunction as a contributor to AD pathology.