Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: FEBS Journal; v. 289, n. 11, p. 18-pg., 2022-01-24.

Resumo

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)

• Processo FAPESP: 18/05350-3 - Investigação do papel da interação entre Mitofusinas e Nek4 na sinalização mitocôndria- núcleo após estresse celular
• Beneficiário: Fernanda Luisa Basei
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/03489-1 - De estudos funcionais à busca de novos inibidores anticâncer: explorando cinases reguladores do ciclo celular da família de NEK humana
• Beneficiário: Jörg Kobarg
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Temático