The unique compactness and economy of gene organization o f the mammalian mitochondrial genome and its very high CCJPY number demand that the regulation of expression of this genome follow unusual rules. Work over the past 10 years in our and other laboratories has identified some of the mechanisms operating in the control of mitochondrial gene expression in mammalian cells in culture and in differentiated mammalian cell systems. As a consequence, a general picture has begun t o emerge concerning the mechanisms by which mammalian cells adapt t o the changing energetic demands in response to functional, developmental and pathological factors.