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Adaptation of skeletal muscle pyruvate dehydrogenase kinase in response to starvation in mitochondrial subpopulations

Pyruvate dehydrogenase (PDH) catalyses 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) sub‐populations. SS and IMF 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 food restriction (FR) on adaptive changes in rat red gastrocnemius muscle PDK2 and 4 isoform content in SS and IMF mitochondria. PDK4 content was 2–4 fold higher in SS mitochondria compared to IMF (p=0.003), and increased with FR ~10‐ fold in both sub‐populations (p<0.001). PDK2 was ~3–4 fold higher in SS mitochondria compared to IMF (p=0.017), but PDK2 was unaltered with FR. These results demonstrate that there is a markedly higher content of both PDK isoforms in SS compared to IMF mitochondria. Although PDK2 does not increase in either sub‐population in response to FR, PDK4 increases to a similar extent in both SS and IMF after 48 h food restriction