Efforts to further characterize the components of the import machinery, to define the role of specific machinery components on the import rate, and to examine protein import function in a variety of mitochondrial diseases are warranted.

Thyroid hormone [3,5,3'-triiodo-l-thyronine (T(3))] induces phenotypic alterations in cardiac mitochondria, in part by influencing protein import and the expression of the import motor mitochondrial heat shock protein (mtHsp70). Here we examined the adaptability of translocases of the inner membrane (Tim) proteins, as well as the outer membrane receptor Tom34, to T(3). Administration of T(3) to rats for 5 days increased cardiac Tim23 and Tim44 mRNA levels by 55 and 50%, respectively, but had no effect on Tim17. T(3) treatment also induced a 45% increase in Tom34 mRNA, with no accompanying changes at the protein level, suggesting regulation at the posttranscriptional level. In H9c2 cardiac cells, Tim17 mRNA was elevated by 114% by 9 days of differentiation, whereas Tim23 and Tim44 declined by 25 and 29%, respectively. To determine the functional consequences of these T(3)-induced changes, malate dehydrogenase (MDH) import rates were measured in H9c2 cells stably overexpressing Tim44 and mtHsp70, either alone or in combination. MDH import remained unaltered in cells overexpressing Tim44 or in cells overexpressing both Tim44 and mtHsp70. However, when mtHsp70 was overexpressed alone, a 13% (P < 0.05) increase in MDH import rate was observed. These findings indicate that import machinery components are differentially regulated in response to stimuli that induce mitochondrial biogenesis, like T(3) and differentiation. In addition, the induction of an import machinery component in response to T(3) may not necessarily result in functional changes in protein import during mitochondrial biogenesis. Finally, mtHsp70 may play a regulatory role in the import process that is independent of its interaction with Tim44.

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Habitual physical activity has long been heralded as a laudable lifestyle behaviour, which can improve overall health and help stave off many major chronic diseases. In spite of substantial scientific evidence and public awareness about the importance of incorporating physical activity into our daily lives, the majority of the North American society remains insufficiently active, failing to meet the minimum requirements set forth by global health authorities. According to the World Health Organization, physical inactivity is now regarded as the 4th leading risk factor for premature death worldwide(1). In fact, recent research suggests that physical inactivity is responsible for approximately 6-10% of the world’s major noncommunicable diseases(2). These pathological conditions - which include cardiovascular disease, type 2 diabetes, and various types of cancers - account for nearly one third of all deaths that occur annually throughout the world, indicating just how important physical activity is in preventing the onset of disease.