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 18772386
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

Investigators with authorship
Erwin BottingerMount Sinai School of Medicine


Malmyelin and lymphocyte protein, T-cell differentiation protein
Mpv17Mpv17 transgene, kidney disease mutant
Htra2HtrA serine peptidase 2
C1scomplement component 1, s subcomponent