INFLUENCE OF AGING ON PROTEIN IMPORT INTO CARDIAC MITOCHONDRIA

This study was undertaken to determine whether age-related changes in the content and composition of cardiac mitochondria could be due, in p art, to alterations in mitochondrial protein import. Precursor protein s malate dehydrogenase and ornithine carbamoyltransferase were synthes ized by in vitro transcription and translation and were incubated with mitochondria isolated from the hearts of young (4-mo), old (22-mo), a nd senescent (28-mo) rats. Mitochondria from senescent animals exhibit ed a twofold higher import rate of both precursors into the matrix com partment compared with mitochondria from young and old animals. The ex pression of glucose regulated protein 75 and heat shock protein 60, tw o matrix chaperonins that are essential for import, was elevated in th e mitochondria of both old and senescent animals before the observed c hanges in import. Import was equally affected in senescent and young h eart mitochondria by inhibition of cardiolipin, a mitochondrial phosph olipid involved in protein translocation. The results indicate that th e altered mitochondrial phenotype evident in the aging myocardium cann ot be accounted for by reduced rates of protein import. Furthermore, l evels of cardiolipin and matrix chaperonins do not appear to be rate-l imiting steps in the import process. These data suggest that the prote in import step of mitochondrial assembly is subject to adaptations und er pathophysiological conditions.