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Mpv17 in mitochondria protects podocytes against mitochondrial dysfunction and apoptosis in vivo and in vitro.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2014 Jun 01; Vol. 306 (11), pp. F1372-80. Date of Electronic Publication: 2014 Mar 05. - Publication Year :
- 2014
-
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 vivo.<br /> (Copyright © 2014 the American Physiological Society.)
- Subjects :
- Animals
Disease Models, Animal
Kidney Glomerulus metabolism
Kidney Glomerulus pathology
Mice
Mice, Transgenic
Mitochondria pathology
Nephritis pathology
Podocytes pathology
Proteinuria metabolism
Proteinuria pathology
Reactive Oxygen Species metabolism
Apoptosis physiology
Membrane Proteins metabolism
Mitochondria metabolism
Nephritis metabolism
Oxidative Stress physiology
Podocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 306
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24598802
- Full Text :
- https://doi.org/10.1152/ajprenal.00608.2013