Tsukamura et al., KNTC1 establishes structural segmentation in mitochondria

Mitochondria contribute to cellular metabolism by providing a specialised milieu for energising cells by incorporating and processing the metabolites. However, a heterogeneity in the mitochondrial structure within is only partially elucidated. Mitochondria dynamically alter their morphology and functions during the life of animals, in which cells execute proliferation and growth. We here show that Kntc1, a highly conserved molecule, exhibits translocation from the Golgi apparatus to mitochondria upon glutamine deprivation and plays an essential role in maintaining mitochondrial linear segments (LMS) in interphase. The Kntc1 localisation in the LMS shows a concomitant increase in the membrane potential, suggesting Kntc1’s role in reserving the energy-generating potential in case starvation persists. Suppression of Kntc1 provokes overuse of glutamine and lactate production, thus impacting cellular metabolism, which leads to anchorage-independent overgrowth of cells. Indeed, the KNTC1 variant was identified in a patient with ovarian cancer, suggesting that regulating mitochondrial metabolism by Kntc1 is essential for maintaining proper cellular status. Our results indicate that functional segmentation of mitochondrial underlies the physiological maintenance of metabolism.