Lon protease homolog, mitochondrial

LONP1 (Lon protease homolog, mitochondrial) is an ATP-dependent serine protease that mediates selective degradation of misfolded, unassembled, and oxidatively damaged polypeptides within the mitochondrial matrix (UniProt: P36776). It also functions in regulating mitochondrial gene expression and genome integrity through site-specific, single-stranded DNA binding. Known substrates include the mitochondrial steroidogenic acute regulatory protein, DELE1, helicase Twinkle, and the large ribosomal subunit protein MRPL32.

LONP1 is implicated in CODAS syndrome (cerebral, ocular, dental, auricular, and skeletal features; MIM 600373), a rare developmental disorder (UniProt: P36776). The protein's roles in mitochondrial proteostasis and DNA regulation suggest broader relevance to cellular dysfunction when disrupted.

In Alzheimer's Disease, LONP1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC = +0.308; Chaparral AD proteomics), consistent with a potential compensatory response to increased mitochondrial protein misfolding and oxidative stress in AD pathology.