Lon peptidase 1, mitochondrial (LonP1)

Lon peptidase 1, mitochondrial (LonP1) is an ATP-dependent serine protease of the mitochondrial matrix, responsible for proteolytic removal of misfolded or damaged proteins, ensuring maintenance of mitochondrial protein homeostasis[1][2][3][4]. It also exhibits chaperone-like activity and binds mitochondrial DNA, playing direct roles in mitochondrial DNA replication and gene expression regulation, including the degradation of TFAM, to maintain mtDNA/TFAM ratios and support mitochondrial biogenesis[1][3]. Disruption or dysregulation of LonP1 activity is linked to multiple human diseases—cancer, neurodegeneration, cardiovascular, and heritable mitochondrial disorders—and LonP1 is under investigation as a therapeutic target[2][3][4]. High expression or mutation can serve as a disease biomarker; however, LonP1 is essential and loss-of-function is not tolerated in mammals[3].\nStructurally, human LONP1 contains substrate recognition, ATPase, and proteolytic domains, and operates as a homohexameric complex, with advanced conformational regulation depending on both substrate and nucleotide binding[1][4].

Other names

Lon protease homolog, mitochondrialLon protease 1LONP1AAA+ Lon proteasePIM1 in yeast (ortholog)La in bacteria (ortholog)

Protease inhibition (prevents degradation of specific mitochondrial proteins, alters protein quality control)\nModulation of mitochondrial function by stabilizing or destabilizing mitochondrial proteostasis and metabolism[2][4]\nMetabolic reprogramming (by influencing the fate of pyruvate and mitochondrial energy balance)[2]