Mitochondrial-Nuclear Communication by Prohibitin Shuttling under Oxidative Stress.
Summary of "Mitochondrial-Nuclear Communication by Prohibitin Shuttling under Oxidative Stress."
Mitochondrial-nuclear communication is critical for maintaining mitochondrial activity under stress conditions. Adaptation of the mitochondrial-nuclear network to changes in the intracellular oxidation and reduction milieu is critical for the survival of retinal and retinal pigment epithelial (RPE) cells, in relation to their high oxygen demand and rapid metabolism. However, the generation and transmission of the mitochondrial signal to the nucleus remain elusive. Previously, our in vivo study revealed that prohibitin is upregulated in the retina, but downregulated in RPE cells in the aging and diabetic model. In this study, the functional role of prohibitin in the retina and RPE cells was examined using biochemical methods, including a lipid binding assay, two-dimensional gel electrophoresis, immunocytochemistry, Western blotting, and a knockdown approach. Protein depletion by siRNA characterized prohibitin as an anti-apoptotic molecule in mitochondria, while the lipid binding assay demonstrated subcellular communication between mitochondria and the nucleus under oxidative stress. The changes in the expression and localization of mitochondrial prohibitin triggered by reactive oxygen species are crucial for mitochondrial integrity. We propose that prohibitin shuttles between mitochondria and the nucleus as an anti-apoptotic molecule and a transcriptional regulator in a stress environment in the retina and RPE cells.
Affiliation
Biological Sciences, Michigan Technological University , Houghton, Michigan 49931, United States.
Journal Details
This article was published in the following journal.
Name: Biochemistry
ISSN: 1520-4995
Pages: 8342-51
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21879722
- DOI: http://dx.doi.org/10.1021/bi2008933
Medical and Biotech [MESH] Definitions
Oxidative Stress
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Venturicidins
Toxic substances isolated from various strains of Streptomyces. They are 20-membered macrolides that inhibit oxidative phosphorylation and mitochondrial ATPases. Venturicidins A and B are glycosides. Used mainly as tools in the study of mitochondrial function.
Protein Carbonylation
The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.
Tert-butylhydroperoxide
A direct-acting oxidative stress-inducing agent used to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. It is also used as a catalyst in polymerization reactions and to introduce peroxy groups into organic molecules.
Mitochondrial Diseases
Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.
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