This focus makes a case that mitophagy is not a straightforward process obeying simple rules. It is a complex process through which the cell gets rid of both damaged and healthy untainted mitochondria to adjust their amount, and in accordance with cellular energy requirements. Several aspects of mitophagy have been described in both yeast and mammalian cells. They have revealed a number of discrepancies in the regulation of this process in the two eukaryotic models. Data have shown that mitophagy is a function of cell physiology. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.