Mitochondria play a key role in adaptation during stressing situations. 
Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is 
expected to be a determinant in this adaptive mechanism since it modulates the 
activity of most membrane proteins. Here, we used Saccharomyces cerevisiae 
subjected to conditions that affect mitochondrial metabolism as a model to 
determine the possible role of cardiolipin in stress adaptation. Interestingly, 
we found that thermal stress promotes a 30% increase in the cardiolipin content 
and modifies the physical state of mitochondrial membranes. These changes have 
effects on mtDNA stability, adapting cells to thermal stress. Conversely, this 
effect is cardiolipin-dependent since a cardiolipin synthase-null mutant strain 
is unable to adapt to thermal stress as observed by a 60% increase of cells 
lacking mtDNA (ρ0). Interestingly, we found that the loss of cardiolipin 
specifically affects the segregation of mtDNA to daughter cells, leading to a 
respiratory deficient phenotype after replication. We also provide evidence that 
mtDNA physically interacts with cardiolipin both in S. cerevisiae and in 
mammalian mitochondria. Overall, our results demonstrate that the mitochondrial 
lipid cardiolipin is a key determinant in the maintenance of mtDNA stability and 
segregation.