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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Mitochondria-localized caveolin in adaptation to cellular stress and injury
FASEB Journal, Volume 26, No. 11, Year 2012
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Description
We show here that the apposition of plasmamembrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings. © FASEB.
Authors & Co-Authors
Fridolfsson, Heidi N.
United States, La Jolla
University of California, San Diego
Kawaraguchi, Yoshitaka
United States, La Jolla
University of California, San Diego
Ali, Sameh S.
United States, La Jolla
University of California, San Diego
Egypt, 6th October
Zewail City of Science and Technology
Panneerselvam, Mathivadhani
United States, La Jolla
University of California, San Diego
Niesman, Ingrid R.
United States, La Jolla
University of California, San Diego
Finley, J. Cameron
United States, La Jolla
University of California, San Diego
Kellerhals, Sarah E.
United States, La Jolla
University of California, San Diego
Migita, Michael Y.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Okada, Hideshi
United States, San Diego
Va San Diego Healthcare System
Moreno, Ana L.
United States, La Jolla
University of California, San Diego
Jennings, Michelle
United States, La Jolla
University of California, San Diego
Kidd, Michael W.
United States, La Jolla
University of California, San Diego
Bonds, Jacqueline A.
United States, La Jolla
University of California, San Diego
Balijepalli, Ravi C.
United States, Madison
University of Wisconsin School of Medicine and Public Health
Ross, Robert S.
United States, San Diego
Va San Diego Healthcare System
Patel, Piyush M.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Miyanohara, Atsushi
Unknown Affiliation
Chen, Qun
United States
Va Medical Center
United States, Richmond
Virginia Commonwealth University
Lesnefsky, Edward J.
United States
Va Medical Center
United States, Richmond
Virginia Commonwealth University
Head, Brian P.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Roth, David M.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Insel, Paul A.
United States, La Jolla
University of California, San Diego
Patel, Hemal H.
United States, La Jolla
University of California, San Diego
United States, San Diego
Va San Diego Healthcare System
Statistics
Citations: 94
Authors: 23
Affiliations: 6
Identifiers
Doi:
10.1096/fj.12-215798
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases
Violence And Injury