Nek4 regulates mitochondrial respiration and morphology

Author(s)

Basei, Fernanda Luisa ; Ferezin, Camila de Castro ; Rodrigues de Oliveira, Ana Luisa ; Munoz, Juan Pablo ; Zorzano, Antonio ; Kobarg, Jorg

• Document type: Journal article
• Source: FEBS Journal; v. 289, n. 11, p. 18-pg., 2022-01-24.

Abstract

Nek4 is a serine/threonine kinase which has been implicated in primary cilia stabilization, DNA damage response, autophagy and epithelial-to-mesenchymal transition. The role of Nek4 in cancer cell survival and chemotherapy resistance has also been shown. However, the precise mechanisms by which Nek4 operates remain to be elucidated. Here, we show that Nek4 overexpression activates mitochondrial respiration coupled to ATP production, which is paralleled by increased mitochondrial membrane potential, and resistance to mitochondrial DNA damage. Congruently, Nek4 depletion reduced mitochondrial respiration and mtDNA integrity. Nek4 deficiency caused mitochondrial elongation, probably via reduced activity of the fission protein DRP1. In Nek4 overexpressing cells, the increase in mitochondrial fission was concomitant to enhanced phosphorylation of DRP1 and Erk1/2 proteins, and the effects on mitochondrial respiration were abolished in the presence of a DRP1 inhibitor. This study shows Nek4 as a novel regulator of mitochondrial function that may explain the joint appearance of high mitochondrial respiration and mitochondrial fragmentation. (AU)

• FAPESP's process: 18/05350-3 - Study of the role of the interaction between mitofusin and Nek4 in the signaling between mitochondria and nucleus after cellular stress
• Grantee: Fernanda Luisa Basei
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/03489-1 - From functional studies to searching for new inhibitors for cancer: exploring kinases that regulate the cell cycle of the human NEK family
• Grantee: Jörg Kobarg
• Support Opportunities: Research Projects - Thematic Grants