Abstract:
University, 2006 Dr. Sandra J. Peters
Pyruvate dehydrogenase (PDH) catalyses the decarboxylation of pyruvate, to
form acetyl-CoA. PDH activity is down-regulated by intrinsic PDH kinases
(predominantly PDK2 and PDK4 isoforms), but the understanding of the PDK isoform
distribution and adaptation to nutritional stresses has been restricted to mixed
mitochondrial populations, and not delineated between subsarcolemmal (SS) and
intermyofibrillar (IMF) subpopulations. SS and IMF mitochondria exhibit distinct
morphological and biochemical properties; however the functional differences are not
well understood. This study investigated the effect of fed (FED) versus 48 h total foodrestriction
(FR) on rat red gastrocnemius muscle PDK2 and 4 isoform content in SS and
IMF mitochondria. PDK4 content was ~3-5 fold higher in SS mitochondria compared to
IMF (p=0.001), and increased with FR -3-4- fold in both subpopulations (p<0.001).
PDK2 was -2.5-4 fold higher in SS mitochondria compared to IMF (p=0.001), but PDK2
was unaltered with FR. Citrate synthase activity (|imol/min/mg mitochondrial protein)
was not different between either subpopulation. As well there were no significant
differences between mitochondrial subpopulations in PDH complex components in both
fed and FR states. These results demonstrate that there is a markedly higher content of
both PDK isofonns in SS compared to IMF mitochondria. Although PDK2 does not
increase in either subpopulation in response to FR, PDK4 increases to a similar extent in
both SS and IMF after 48 h food-restriction.
