Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and
apoptosis in vivo and in vitro.
Authors Casalena G, Krick S, Daehn I, Yu L, Ju W, Shi S, Tsai SY, D'Agati V, Lindenmeyer
M, Cohen CD, Schlondorff D, Bottinger EP
Submitted By Erwin Bottinger on 8/5/2014
Status Published
Journal American journal of physiology. Renal physiology
Year 2014
Date Published 6/1/2014
Volume : Pages 306 : F1372 - F1380
PubMed Reference 24598802
Abstract Mitochondrial dysfunction is increasingly recognized as contributing to
glomerular diseases, including those secondary to mitochondrial DNA (mtDNA)
mutations and deletions. Mitochondria maintain cellular redox and energy
homeostasis and are a major source of intracellular reactive oxygen species
(ROS) production. Mitochondrial ROS accumulation may contribute to
stress-induced mitochondrial dysfunction and apoptosis and thereby to
glomerulosclerosis. In mice, deletion of the gene encoding Mpv17 is associated
with glomerulosclerosis, but the underlying mechanism remains poorly defined.
Here we report that Mpv17 localizes to mitochondria of podocytes and its
expression is reduced in several glomerular injury models and in human focal
segmental glomerulosclerosis (FSGS) but not in minimal change disease. Using
models of mild or severe nephrotoxic serum nephritis (NTSN) in Mpv17(+/+)
wild-type (WT) and Mpv17(-/-) knockout mice, we found that Mpv17 deficiency
resulted in increased proteinuria (mild NTSN) and renal insufficiency (severe
NTSN) compared with WT. These lesions were associated with increased
mitochondrial ROS generation and mitochondrial injury such as oxidative DNA
damage. In vitro, podocytes with loss of Mpv17 function were characterized by
increased susceptibility to apoptosis and ROS injury including decreased
mitochondrial function, loss of mtDNA content, and change in mitochondrial
configuration. In summary, the inner mitochondrial membrane protein Mpv17 in
podocytes is essential for the maintenance of mitochondrial homeostasis and
protects podocytes against oxidative stress-induced injury both in vitro and in

Investigators with authorship
Erwin BottingerMount Sinai School of Medicine