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Article: Prohibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility

TitleProhibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility
Authors
Keywordsmale infertility
prohibitin (PHB)
protein kinase B (AKT)
sperm motility
Issue Date2020
PublisherMedknow Publications. The Journal's web site is located at http://www.asiaandro.com
Citation
Asian Journal of Andrology, 2020, v. 22 n. 6, p. 583-589 How to Cite?
AbstractProhibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.
Persistent Identifierhttp://hdl.handle.net/10722/295776
ISSN
2020 Impact Factor: 3.285
2015 SCImago Journal Rankings: 0.879
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, XH-
dc.contributor.authorChai, RR-
dc.contributor.authorChen, GW-
dc.contributor.authorZhang, LF-
dc.contributor.authorTan-Tai, WJ-
dc.contributor.authorShi, HJ-
dc.contributor.authorMartin-DeLeon, PA-
dc.contributor.authorO, WS-
dc.contributor.authorChen, H-
dc.date.accessioned2021-02-08T08:13:51Z-
dc.date.available2021-02-08T08:13:51Z-
dc.date.issued2020-
dc.identifier.citationAsian Journal of Andrology, 2020, v. 22 n. 6, p. 583-589-
dc.identifier.issn1008-682X-
dc.identifier.urihttp://hdl.handle.net/10722/295776-
dc.description.abstractProhibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.-
dc.languageeng-
dc.publisherMedknow Publications. The Journal's web site is located at http://www.asiaandro.com-
dc.relation.ispartofAsian Journal of Andrology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmale infertility-
dc.subjectprohibitin (PHB)-
dc.subjectprotein kinase B (AKT)-
dc.subjectsperm motility-
dc.titleProhibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.4103/aja.aja_46_20-
dc.identifier.pmid32859869-
dc.identifier.pmcidPMC7705974-
dc.identifier.hkuros321230-
dc.identifier.volume22-
dc.identifier.issue6-
dc.identifier.spage583-
dc.identifier.epage589-
dc.identifier.isiWOS:000588442200007-
dc.publisher.placeIndia-

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