Biogenesis of the mitochondrial Tom40 channel in skeletal muscle from aged animals and its adaptability to chronic contractile activity.
Evidence exists that mitochondrial content and/or function is reduced in muscle of aging individuals. The purposes of this study were to investigate the contribution of outer membrane protein import and assembly processes to this decline and to determine whether the assembly process could adapt to chronic contractile activity (CCA). Tom40 assembly into the translocases of the outer membrane (TOM complex) was measured in subsarcolemmal mitochondria obtained from young (6 mo old) and aged (36 mo old) Fischer 344 x Brown Norway animals. While the initial import of Tom40 did not differ between young and aged animals, its subsequent assembly into the final approximately 380 kDa complex was 2.2-fold higher (P < 0.05) in mitochondria from aged compared with young animals. This was associated with a higher abundance of Tom22, a protein vital for the assembly process. CCA induced a greater initial import and subsequent assembly of Tom40 in mitochondria from young animals, resulting in a CCA-induced 75% increase (P < 0.05) in Tom40 within mitochondria. This effect of CCA was attenuated in mitochondria from old animals. These data suggest that the import and assembly of proteins into the outer membrane do not contribute to reduced mitochondrial content or function in aged animals. Indeed, the greater assembly rate in mitochondria from aged animals may be a compensatory mechanism attempting to offset any decrements in mitochondrial content or function within aged muscle. Our data also indicate the potential of CCA to contribute to increased mitochondrial biogenesis in muscle through changes in the outer membrane import and assembly pathway.
Joseph
Anna-Maria
AM
School of Kinesiology and Health Science, York Univesity, Toronto, ON, Canada.
Ljubicic
Vladimir
V
Adhihetty
Peter J
PJ
Hood
David A
DA
D000222:Adaptation, Physiological; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003433:Crosses, Genetic; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D055503:Protein Multimerization; D021381:Protein Transport; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; C530938:TOMM22 protein, rat; C000707766:Tomm40 protein, rat