Mitochondria contribute to cellular metabolism by providing a specialised milieu for energising cells by incorporating and processing the metabolites. However, heterogeneity in the mitochondria within is only partially elucidated. Mitochondria dynamically alter their morphology and functions during the life of animals, in which cells proliferate and grow. We here show that Kntc1, a highly evolutionarily conserved protein, translocates from the Golgi apparatus to linear mitochondrial segments (LMS) upon glutamine deprivation and plays an essential role in maintaining LMS. The LMS with Kntc1 localisation exhibits an increase in the membrane potential, suggesting the role of Kntc1 in functioning as a reservoir for the energy-generating potential. Suppression of Kntc1 leads to glutamine consumption and lactate production, thus impacting cellular metabolism, eventually leading to anchorage-independent growth of cells. Indeed, the KNTC1 variant was identified in a patient with ovarian cancer, suggesting that segmental regulation of the mitochondrial function is essential for maintaining tissue integrity.
KNTC1 introduces segmental heterogeneity to mitochondria
- Award Group:
- Funder(s): Japan Health Research Promotion Bureau
- Award Id(s): 2021-B-01
- Funder(s):
- Award Group:
- Funder(s): Japan Society for the Promotion of Science
- Award Id(s): 22K19499,JP23H02829,JP24K02230
- Funder(s):
- Award Group:
- Funder(s): Japan Agency for Medical Research and Development
- Award Id(s): JP22gm6710009
- Funder(s):
- Award Group:
- Funder(s): Takeda Science Foundation
- Funder(s):
Atsushi Tsukamura, Hirotaka Ariyama, Natsuki Hayashi, Satoko Miyatake, Satoko Okado, Sara Sultana, Ichiro Terakado, Takefumi Yamamoto, Shoji Yamanaka, Satoshi Fujii, Haruka Hamanoue, Ryoko Asano, Taichi Mizushima, Naomichi Matsumoto, Yoshihiro Maruo, Masaki Mori; KNTC1 introduces segmental heterogeneity to mitochondria. Dis Model Mech 2025; dmm.052063. doi: https://doi.org/10.1242/dmm.052063
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