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Publication

Mpv17l protects cells against mitochondrial dysfunction and apoptosis through its regulation of Omi/HtrA2

Authors Stefanie Krick, Shaolin Shi, Wenjun Ju, Peter H Mundel and Erwin P Bottinger Submitted By Erwin Bottinger on 11/9/2007 Status Published Journal Proceedings of the National Academy of Sciences of the United States of America Year 2008 Date Published 9/16/2008 Volume : Pages 105 : 14106 - 14111 PubMed Reference Abstract The Mpv17-like-protein (Mpv17l) is a novel member of the Mpv17/PMP22 protein family. Mpv17l exists in two isoforms and has high sequence homology with the inner mitochondrial membrane protein Mpv17, absence or malfunction of which causes oxidative phosphorylation failure and mitochondrial DNA depletion syndrome in mice and humans1. In contrast to what previously reported, both Mpv17l isoforms are localized in mitochondria. Results from both in vivo and in vitro experiments show that Mpv17l is down-regulated by ROS-generating extracellular signals. Such modulation leads to increased mitochondrial superoxide generation, which results in depolarization of the inner mitochondrial membrane potential and increased apoptosis. Furthermore, we show that the anti-apoptotic effect of Mpv17l is mediated by its direct interaction with the mitochondrial serine protease Omi/HtrA2. Our findings identify the Mpv17l-Omi/HtrA2 heterodimer as a novel ROS sensor/effector complex that protects cells against ROSinduced apoptosis by reducing mitochondrial oxidative stress.

Investigators with authorship
Name Institution Erwin Bottinger Mount Sinai School of Medicine

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing

Genes
Symbol Description Mal myelin and lymphocyte protein, T-cell differentiation protein Mpv17 Mpv17 transgene, kidney disease mutant Ucn urocortin Htra2 HtrA serine peptidase 2 C1s complement component 1, s subcomponent