Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology.
Remodeling of mitochondria is a dynamic process coordinated by fusion and fission of the inner and outer membranes of the organelle, mediated by a set of conserved proteins. In metazoans, the molecular mechanism behind mitochondrial morphology has been recruited to govern novel functions, such as development, calcium signaling, and apoptosis, which suggests that novel mechanisms should exist to regulate the conserved membrane fusion/fission machinery. Here we show that phosphorylation and cleavage of the vertebrate-specific Pbeta domain of the mammalian presenilin-associated rhomboid-like (PARL) protease can influence mitochondrial morphology. Phosphorylation of three residues embedded in this domain, Ser-65, Thr-69, and Ser-70, impair a cleavage at position Ser(77)-Ala(78) that is required to initiate PARL-induced mitochondrial fragmentation. Our findings reveal that PARL phosphorylation and cleavage impact mitochondrial dynamics, providing a blueprint to study the molecular evolution of mitochondrial morphology.
Jeyaraju
Danny V
DV
Centre de Recherche Université Laval Robert-Giffard, 2601 ch. de la Canardière, Quebec City, QC, Canada G1J 2G3.
Xu
Liqun
L
Letellier
Marie-Claude
MC
Bandaru
Sirisha
S
Zunino
Rodolfo
R
Berg
Eric A
EA
McBride
Heidi M
HM
Pellegrini
Luca
L
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry* / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D053763:Presenilins / Q000378:metabolism
D024101:Mitochondrial Proteins; D053763:Presenilins; D045726:Metalloproteases; C485223:PARL protein, human