Clustered mitochondria protein homolog

CLUH (Clustered mitochondria protein homolog) is an mRNA-binding protein that regulates cytoplasmic distribution of mitochondria by binding to transcripts encoding nuclear-encoded mitochondrial proteins and directing their transport or translation near mitochondria (UniProt: O75153). This function supports mitochondrial biogenesis and proper cellular energy metabolism.

CLUH localizes to the cytoplasm where it modulates mitochondrial positioning and protein synthesis, processes essential for neuronal bioenergetics. The protein has no explicitly documented disease associations in UniProt, but its role in mitochondrial function implicates it in cellular stress responses.

In Alzheimer's Disease, CLUH is downregulated in post-mortem brain tissue compared to age-matched controls (mean log2 fold-change: −0.44, Chaparral AD proteomics). This reduction was detected across a single subcellular fraction in a TMT-labeled proteomic study of four compartments (P2, P3, S2, S3) from human brain homogenates. Decreased CLUH expression may impair mitochondrial biogenesis and distribution, potentially exacerbating the mitochondrial dysfunction and energy deficits characteristic of AD pathology.