KNTC1 introduces segmental heterogeneity to mitochondria

TL;DR

The protein KNTC1 helps regulate mitochondrial segments, affecting energy production and potentially contributing to cancer.

Contribution

KNTC1 is identified as a glutamine sensor that introduces mitochondrial segmental heterogeneity.

Findings

Kntc1 translocates to linear mitochondrial segments under glutamine deprivation.

Kntc1 maintains mitochondrial membrane potential and affects cellular metabolism.

A KNTC1 variant was found in ovarian cancer, linking mitochondrial regulation to tissue integrity.

Abstract

Mitochondria contribute to cellular metabolism by providing a specialised milieu for energising cells by incorporating and processing the metabolites. However, heterogeneity between mitochondria has only partially been elucidated. Mitochondria dynamically alter their morphology and function during the life of an animal, when cells proliferate and grow. We here show that Kntc1, a highly evolutionarily conserved protein, translocates from the Golgi apparatus to linear mitochondrial segments (LMSs) upon glutamine deprivation and plays an essential role in maintaining LMSs. The LMSs to which Kntc1 localised exhibited an increase in the mitochondrial membrane potential, suggesting the role of Kntc1 in functioning as a reservoir for the energy-generating potential. Suppression of Kntc1 led to glutamine consumption and lactate production, thus impacting cellular metabolism, eventually leading to anchorage-independent growth of cells. Indeed, a KNTC1 variant was identified in a patient with ovarian cancer, suggesting that segmental regulation of the mitochondrial function is essential for maintaining tissue integrity.

Summary: Mitochondria possess structural and functional heterogeneities between them, which is established by the glutamine sensor KNTC1

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