Article ID Journal Published Year Pages File Type
2038070 Cell 2006 13 Pages PDF
Abstract

SummaryRhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. Presenilin-associated rhomboid-like (PARL) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. Parl−/− mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic atrophy leading to cachectic death. Atrophy is sustained by increased apoptosis, both in and ex vivo. Parl−/− cells display normal mitochondrial morphology and function but are no longer protected against intrinsic apoptotic death stimuli by the dynamin-related mitochondrial protein OPA1. Parl−/− mitochondria display reduced levels of a soluble, intermembrane space (IMS) form of OPA1, and OPA1 specifically targeted to IMS complements Parl−/− cells, substantiating the importance of PARL in OPA1 processing. Parl−/− mitochondria undergo faster apoptotic cristae remodeling and cytochrome c release. These findings implicate regulated intramembrane proteolysis in controlling apoptosis.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry, Genetics and Molecular Biology (General)
Authors
, , , , , , , , , , , , , , ,