Recombinant Human Lon protease homolog, mitochondrial (LONP1), partial

Function

ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix (PubMed:12198491, PubMed:15870080, PubMed:17579211, PubMed:37327776, PubMed:8248235, PubMed:35870450, PubMed:38688959). Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, DELE1, helicase Twinkle (TWNK) and the large ribosomal subunit protein MRPL32/bL32m (PubMed:17579211, PubMed:28377575, PubMed:37327776). MRPL32/bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not (PubMed:17579211, PubMed:28377575). In addtion to its protease activity, has also an ATP-dependent protein folding chaperone activity and functions in mitochondrial protein folding (PubMed:33431889). Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome (PubMed:17420247). Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner (PubMed:17420247). May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters (PubMed:14739292, PubMed:17420247)

Subcellular Location

Mitochondrion matrix

Disease Association

CODAS syndrome (CODASS) : A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Duodenum, heart, lung and liver, but not thymus

Subunit

Homohexamer (PubMed:14739292, PubMed:20222013, PubMed:25369343, PubMed:38688959, PubMed:35870450). Organized in a ring with a central cavity (PubMed:20222013, PubMed:25369343). The ATP-binding and proteolytic domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers (PubMed:27632940). DNA and RNA binding is stimulated by substrate and inhibited by ATP binding. Interacts with TWNK and mitochondrial DNA polymerase subunit POLG (PubMed:14739292)

• Wang N. et al. A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease. — Proc. Natl. Acad. Sci. U.S.A. (1993)
• Wang W. et al. Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. — Nucleic Acids Res. (2011)
• Huang N.N. et al. Chromosomal mapping and genomic organization of the ATP-dependent human LON protease gene. (APR-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Grimwood J. et al. The DNA sequence and biology of human chromosome 19. — Nature (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Amerik A.Y. et al. Cloning and sequence analysis of cDNA for a human homolog of eubacterial ATP-dependent Lon proteases. — FEBS Lett. (1994)