Mitochondrial fusion and fission are actively regulated during metabolic, differentiation and activation challenges in cells. In Cell, Buck et al. show that fused mitochondrial networks in memory T cells (TM cells) are associated with enhanced oxidative phosphorylation, fatty-acid oxidation and memory-like characteristics. Effector T cells (TE cells) have punctate mitochondria and activate the fission factor Drp1, whereas TM cells have tubular mitochondria and high expression of the fusion mediators Opa1 and Mfn2. Opa1-deficient naive T cells generate normal TE cells but markedly impaired TM cell responses, while enforced mitochondrial fusion in TE cells increases fatty-acid oxidation, production of interferon-g and TNF, and cell longevity after adoptive transfer of the cells. The mitochondria of TM cells have tighter cristae in the mitochondrial membrane than those of TE cells, suggestive of more closely associated electron-transport-chain complexes, which might correlate with more efficient oxidative phosphorylation.
Cell 166, 63–67 (2016)