LONP1
Description
The LONP1 (lon peptidase 1, mitochondrial) is a protein-coding gene located on chromosome 19.
LONP1, the gene encoding the mitochondrial Lon protease homolog, is a crucial component of mitochondrial protein quality control. This protease, a member of the ATP-dependent proteases (AAA+ proteases), plays a vital role in maintaining mitochondrial function. LONP1's active form is a homohexamer, consisting of six identical subunits. Each subunit comprises three distinct domains: the N-domain for substrate recognition, the AAA+ module (A-domain) for ATP binding and hydrolysis, and the P-domain for proteolysis. The enzyme's primary function is the degradation of unfolded or misfolded proteins within the mitochondrial matrix, ensuring proper protein homeostasis. However, LONP1's responsibilities extend beyond protein degradation. Its chaperone activity assists in the assembly of inner membrane protein complexes, and its interaction with mitochondrial DNA (mtDNA) influences mtDNA replication and transcription. LONP1 binds specifically to promoters within the mtDNA, suggesting a regulatory role in gene expression. Notably, LONP1's activity is tightly regulated, as it can bind DNA and RNA, with its binding enhanced by the presence of substrate and inhibited by ATP. This complex interplay highlights LONP1's multifaceted role in maintaining mitochondrial integrity.
LONP1 is an ATP-dependent serine protease that selectively degrades misfolded, unassembled, or oxidatively damaged proteins, as well as certain short-lived regulatory proteins, within the mitochondrial matrix. It targets a range of endogenous substrates, including mitochondrial steroidogenic acute regulatory (StAR) protein, DELE1, helicase Twinkle (TWNK), and the large ribosomal subunit protein MRPL32/bL32m. Interestingly, MRPL32/bL32m is protected from degradation by LONP1 when bound to nucleic acid (RNA), while TWNK is not. Beyond its proteolytic function, LONP1 might also act as a chaperone in the assembly of inner membrane protein complexes. It plays a crucial role in regulating mitochondrial gene expression and maintaining the integrity of the mitochondrial genome. LONP1 binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. This binding suggests a potential regulatory mechanism for mitochondrial DNA replication and gene expression, where LONP1 targets the degradation of regulatory proteins bound to adjacent sites in mitochondrial promoters.
LONP1 is also known as CODASS, LON, LONP, LonHS, PIM1, PRSS15, hLON.
