Recombinant Human Presenilins-associated rhomboid-like protein, mitochondrial (PARL) Protein

Function

Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Promotes cleavage of serine/threonine-protein phosphatase PGAM5 in damaged mitochondria in response to loss of mitochondrial membrane potential (PubMed:22915595). Mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria, disassociating from PINK1 and associating with PGAM5 in response to mitochondrial membrane potential loss (PubMed:22915595). Required for processing of CLPB into a form with higher protein disaggregase activity by removing an autoinhibitory N-terminal peptide (PubMed:28288130, PubMed:32573439). Promotes processing of DIABLO/SMAC in the mitochondrion which is required for DIABLO apoptotic activity (PubMed:28288130). Mediates STARD7 processing which regulates STARD7 location between mitochodria and cytosol (PubMed:28288130, PubMed:29301859, PubMed:36658222). Also required for cleavage of TTC19 (PubMed:28288130). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872)

Subcellular Location

Nucleus

Subunit

Interacts with PSEN1 and PSEN2. Binds OPA1

• Pellegrini L. et al. PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of presenilin-1 and -2. — J. Alzheimers Dis. (2001)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Zhang C. et al. Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver. (DEC-)
• Sik A. et al. Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease PARL yields Pbeta, a nuclear-targeted peptide. — J. Biol. Chem. (2004)
• Jeyaraju D.V. et al. Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology. — Proc. Natl. Acad. Sci. U.S.A. (2006)
• Greene A.W. et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. — EMBO Rep. (2012)
• Sekine S. et al. Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM5. — J. Biol. Chem. (2012)
• Saita S. et al. PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis. — Nat. Cell Biol. (2017)