Mitochondria are highly dynamic and undergo fission and fusion in response to the cell status in order to maintain homeostasis. For instance, in myopathies, mitochondria are often found fragmented, or show altered distribution. To investigate how mitochondria behaviour is affected by physiological stresses, Manuela Lavorato and colleagues determine here (Lavorato et al., 2018) the ultrastructural changes in mitochondria in response to muscle fatigue. To that end, they subjected mice to either running on treadmills to exhaustion, or electrical stimulation of their sciatic nerve, before analysing the fast-twitch type IIB/IIX muscle fibres that are most prone to fatigue. The authors discovered the narrowing of mitochondria with the appearance of elongated mitochondrial constrictions (EMCs) that are closely associated with sarcoplasmic reticulum (SR) elements and have not been reported before. Indeed, EMCs occur only very rarely in resting muscle and thus might have been overlooked in the past. Moreover, the authors show an increased recruitment of the Ser 616-phosphorylated form of Drp1, which is known to promote fission, to the mitochondrial membrane upon fatigue. This might indicate a mitochondrial stress response, resulting in long-lasting fission events, and further work will be needed to address in more detail the role of Drp1 in the regulation of bioenergetics under physiological conditions.
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