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Mitochondria‐localized caveolin in adaptation to cellular stress and injury
Author(s) -
Fridolfsson Heidi N.,
Kawaraguchi Yoshitaka,
Ali Sameh S.,
Panneerselvam Mathivadhani,
Niesman Ingrid R.,
Finley J. Cameron,
Kellerhals Sarah E.,
Migita Michael Y.,
Okada Hideshi,
Moreno Ana L.,
Jennings Michelle,
Kidd Michael W.,
Bonds Jacqueline A.,
Balijepalli Ravi C.,
Ross Robert S.,
Patel Piyush M.,
Miyanohara Atsushi,
Chen Qun,
Lesnefsky Edward J.,
Head Brian P.,
Roth David M.,
Insel Paul A.,
Patel Hemal H.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-215798
Subject(s) - caveolae , mitochondrion , microbiology and biotechnology , caveolin 3 , biology , caveolin 1 , caenorhabditis elegans , chemistry , biochemistry , signal transduction , gene
We show here that the apposition of plasma membrane 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.—Fridolfsson, H. N., Kawaraguchi, Y., Ali, S. S., Panneerselvam, M., Niesman, I. R., Finley, J. C., Kellerhals, S. E., Migita, M. Y., Okada, H., Moreno, A. L., Jennings, M., Kidd, M. W., Bonds, J. A., Balijepalli, R. C., Ross, R. S., Patel, P. M., Miyanohara, A., Chen, Q., Lesnefsky, E. J., Head, B. P., Roth, D. M., Insel, P. A., Patel, H. H. Mitochondria‐localized caveolin in adaptation to cellular stress and injury. FASEB J. 26, 4637–4649 (2012). www.fasebj.org