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Cardiac Aging Concurs With Abnormal Mitochondrial Metabolism, Calcium Handling and Disrupted Levels of Mitochondrial Calcium Uniporter Complex Member Proteins
Author(s) -
Suarez Jorge,
DiazJuarez Julieta,
Scott Brian T.,
Dai Anzhi,
Dillmann Wolfgang H.
Publication year - 2016
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/fasebj.30.1_supplement.1015.13
Subject(s) - uniporter , calcium , mitochondrion , western blot , calcium metabolism , chemistry , calcium binding protein , cardiac function curve , medicine , endocrinology , mitochondrial matrix , metabolism , biology , biochemistry , heart failure , gene , cytosol , enzyme
Cardiac aging results in impaired cardiac function along with mitochondrial (Mito) dysfunction. The mechanisms for diminished function of the aging heart are incompletely investigated. Mito metabolism is regulated by free calcium concentration ([Ca 2+ ]m) in the mitochondrial matrix. The Mito calcium uniporter complex (MCUC) is the main calcium transporter in the mitochondria. We hypothesized that Mito dysfunction could be the result of aging‐induced maladaptive changes in protein levels of the MCUC that results in deficient Mito Ca 2+ handling that, in turn, impairs Mito metabolism. Therefore, the objective of this work was to determine the protein levels of members of the MCUC and analyze Mito Ca 2+ handling as well as glucose oxidation (Gox). We measured protein levels by Western blot of MCU, MCUb, EMRE and MICU1/2 in hearts of young (2–3 months) and old (19–22 months) mice. In addition, we analyzed Mito Ca 2+ uptake, release, and [Ca 2+ ]m using Mito pericam. Gox was measured in an isolated “working heart” preparation. Our results showed that MCU and EMRE, which stimulate Ca 2+ import, are decreased by 22% and 83% in hearts from old mice, respectively. In addition, MCUb which inhibits Ca 2+ import is increased by 65% with no changes in MICU1/2. Furthermore, Mito Ca 2+ uptake and [Ca 2+ ]m were decreased by 35% and 37%, respectively. These effects of aging on Mito Ca 2+ handling were consistent with reduced Gox by 45% that we measured in hearts from old mice. In conclusion, aging is associated with abnormal Mito Ca 2+ handling produced by decrease in proteins of the MCUC that stimulate Mito Ca 2+ uptake and increase in expression of MCUb, which inhibits Mito Ca 2+ uptake. These maladaptive changes in aging result in impaired Mito metabolism and reduced Mito function in the heart. Support or Funding Information This work was supported by National Institutes of Health grants (5 P01 HL066941‐13), with a Merit Review Award from the Department of Veteran's Affairs (5 I01BX001121‐02) and the P. Robert Majumder Charitable Foundation. Diaz‐Juarez J. received support from UCMEXUS‐CONACYT.