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.