ATP-dependent clpX-like chaperone, mitochondrial

CLPX (ATP-dependent clpX-like chaperone, mitochondrial) is a mitochondrial AAA+ ATPase that functions as an unfoldase within the ClpXP protease complex (UniProt: O76031). It recognizes protein substrates, unfolds them using ATP hydrolysis, and delivers them to the CLPP protease for degradation. Additionally, CLPX activates heme biosynthesis by facilitating pyridoxal phosphate incorporation into 5-aminolevulinate synthase and regulates mitochondrial transcription factor A to control mtDNA nucleoid organization.

CLPX is localized to mitochondria and plays a critical role in proteostasis and metabolic cofactor metabolism. UniProt documents an association with erythropoietic protoporphyria 2 (EPP2; MIM 618015), an autosomal dominant porphyria caused by defective heme biosynthesis (UniProt: O76031).

In Alzheimer's disease, CLPX is significantly upregulated in post-mortem AD brain compared to age-matched controls (mean log2 fold-change: 0.27; Chaparral AD proteomics). This elevation suggests potential compensatory mitochondrial quality control responses in AD pathology, though the functional significance of increased CLPX in AD neurodegeneration requires further investigation.