Journal
FEBS OPEN BIO
Volume 11, Issue 3, Pages 546-563Publisher
WILEY
DOI: 10.1002/2211-5463.13108
Keywords
LonP1; mitochondria; mtDNA; NEK kinases; NEK5; TFAM
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/50938-8, 2017/03489-1, 2016/10530-5, 2018/05350-3]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [465699/2014-6, 573913/2008-0]
- Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES) [001]
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NEK5 plays a role in regulating mitochondrial homeostasis and mtDNA maintenance, with its kinase activity being necessary for maintaining mitochondrial mass, functionality, and mtDNA integrity. The interaction between NEK5 and LonP1 may be crucial for these processes.
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.
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