{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:13Z","timestamp":1785413653535,"version":"3.56.0"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Fapesp","doi-asserted-by":"crossref","award":["2017\/03489-1"],"award-info":[{"award-number":["2017\/03489-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"Fapesp","doi-asserted-by":"crossref","award":["2022\/15126-9"],"award-info":[{"award-number":["2022\/15126-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"Fapesp","doi-asserted-by":"crossref","award":["CNPq 404029\/2023-2"],"award-info":[{"award-number":["CNPq 404029\/2023-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"Fapesp","doi-asserted-by":"crossref","award":["CNPq 306427\/2021-4"],"award-info":[{"award-number":["CNPq 306427\/2021-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2017\/03489-1"],"award-info":[{"award-number":["2017\/03489-1"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2022\/15126-9"],"award-info":[{"award-number":["2022\/15126-9"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CNPq 404029\/2023-2"],"award-info":[{"award-number":["CNPq 404029\/2023-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CNPq 306427\/2021-4"],"award-info":[{"award-number":["CNPq 306427\/2021-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The family of Nek kinases has 11 human members that are conserved in their kinase domains but diverse in their regulatory domains. Functionally, they can be associated with diverse aspects of cell cycle regulation, from mitosis and primary cilia function to centrosome disjunction in the G2 phase and checkpoints of the DNA damage response. However, novel functional contexts have emerged in recent years, including regulatory roles of Neks 1, 4, 5, and 10 in mitochondrial metabolic and morphological homeostasis. We recently generated, by CRISPR-Cas9 technology, a DU-145 prostate cancer cell line, with an NEK6 gene knockout. Here, we focus on a detailed characterization of changes in this cell line, in mitochondrial respiration function and morphology. DU-145 NEK6 knockout cells exhibited reduced mitochondrial respiration and a fragmented phenotype in electron microscopy, with reduced mitochondrial cristae numbers. Alterations in mitochondrial architecture and respiration were correlated with increased expression of anaerobic glycolytic proteins (HK2, PFKP, and LDHA) and decreased expression of PDH, an enzyme of aerobic glycolysis. Molecular analysis by Western blot revealed decreased levels of mitochondrial mass and biogenesis protein markers (TOM20, TFAM), without alterations in other markers such as VDAC1\/3 or mtDNA copy number in the NEK6 knockout cells. Furthermore, the regulators of mitochondrial fusion\/fission are altered in the knockout cells (decrease in the Long-OPA1:Short-OPA1 ratio and DRP1 total level), which is associated with an increase in endoplasmic reticulum\u2013mitochondria contact at \u226420 nm observed in transmission electron microscopy (TEM) image analysis. Using analysis of TEM micrographs, we found an increase in the autophagic structures (autophagosome, amphisome, and autolysosome), with mitochondria as cargo in some structures, which was correlated with a decrease in LC3A\/B and an increase in the BECLIN1 total level, and with an increase in acidic vesicles approximation, suggesting that reduction in TOM20 and TFAM without alterations in VDAC1\/3 and mtDNA copy number might be related to mitochondrial degradation through autophagy. Together, our data suggest a new role for NEK6 in regulating mitochondrial homeostasis, where its loss alters mitochondrial morphology and respiration, and could be associated with an increase in the degradation of the dysfunctional mitochondria through autophagy.<\/jats:p>","DOI":"10.3390\/cells15100924","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NEK6 Knockout Causes Defects in Mitochondrial Morphology and Respiration"],"prefix":"10.3390","volume":"15","author":[{"given":"Fernando Riback da","family":"Silva","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Rafael Firmino","family":"Dias","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora Carolina Betim","family":"Pavan","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa Peres de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-7170","authenticated-orcid":false,"given":"Fernanda Luisa","family":"Basei","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Ester dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-402X","authenticated-orcid":false,"given":"Lizandra Maia de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-021X","authenticated-orcid":false,"given":"S\u00edlvio Roberto","family":"Consonni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Gustavo de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Reis","family":"Silveira","sequence":"additional","affiliation":[{"name":"Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-0145","authenticated-orcid":false,"given":"J\u00f6rg","family":"Kobarg","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Basei, F.L., e Silva, I.R., Dias, P.R.F., Ferezin, C.C., Peres de Oliveira, A., Issayama, L.K., Moura, L.A.R., da Silva, F.R., and Kobarg, J. 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