NEK5 interacts with LonP1 and its kinase activity is essential for the regulation of mitochondrial functions and mtDNA maintenance

Author(s)

Ferezin, Camila de Castro ^{[1, 2]} ; Basei, Fernanda Luisa ^{[1, 2]} ; Melo-Hanchuk, Talita D. ^[2] ; de Oliveira, Ana Luisa ^[1] ; Peres de Oliveira, Andressa ^[2] ; Mori, Mateus P. ^[3] ; de Souza-Pinto, Nadja C. ^[3] ; Kobarg, Jorg ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Ciencias Farmaceut, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

• Document type: Journal article
• Source: FEBS OPEN BIO; v. 11, n. 3 FEB 2021.
• Web of Science Citations: 0

Abstract

Little is known about Nima-related kinase (NEKs), a widely conserved family of kinases that have key roles in cell-cycle progression. Nevertheless, it is now clear that multiple NEK family members act in networks, not only to regulate specific events of mitosis, but also to regulate metabolic events independently of the cell cycle. NEK5 was shown to act in centrosome disjunction, caspase-3 regulation, myogenesis, and mitochondrial respiration. Here, we demonstrate that NEK5 interacts with LonP1, an AAA+ mitochondrial protease implicated in protein quality control and mtDNA remodeling, within the mitochondria and it might be involved in the LonP1-TFAM signaling module. Moreover, we demonstrate that NEK5 kinase activity is required for maintaining mitochondrial mass and functionality and mtDNA integrity after oxidative damage. Taken together, these results show a new role of NEK5 in the regulation of mitochondrial homeostasis and mtDNA maintenance, possibly due to its interaction with key mitochondrial proteins, such as LonP1. (AU)

• FAPESP's process: 16/10530-5 - The funtion of the protein kinase Nek5 in normal and cancer cells: from the identification of physiological substrates to inhibitor design
• Grantee: Camila de Castro Ferezin
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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
• 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: 14/50938-8 - INCT 2014: in Photonics Applied to Cell Biology
• Grantee: Hernandes Faustino de Carvalho
• Support Opportunities: Research Projects - Thematic Grants