Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells

Abstract Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitoch...

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Autores principales:	Timo N. Haschler, Harry Horsley, Monika Balys, Glenn Anderson, Jan-Willem Taanman, Robert J. Unwin, Jill T. Norman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf7c614184604ba8a7792b2421c0cbc7
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spelling	oai:doaj.org-article:bf7c614184604ba8a7792b2421c0cbc72021-12-02T16:24:22ZSirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells10.1038/s41598-021-94185-62045-2322https://doaj.org/article/bf7c614184604ba8a7792b2421c0cbc72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94185-6https://doaj.org/toc/2045-2322Abstract Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI. The mitochondrial NAD+-dependent enzyme sirtuin 5 (SIRT5) is a key regulator of mitochondrial form and function, but its role in ischemic renal injury (IRI) is unknown. SIRT5 expression was increased in murine PTECs after IRI in vivo and in human PTECs (hPTECs) exposed to an oxygen/nutrient deprivation (OND) model of IRI in vitro. SIRT5-depletion impaired ATP production, reduced mitochondrial membrane potential, and provoked mitochondrial fragmentation in hPTECs. Moreover, SIRT5 RNAi exacerbated OND-induced mitochondrial bioenergetic dysfunction and swelling, and increased degradation by mitophagy. These findings suggest SIRT5 is required for normal mitochondrial function in hPTECs and indicate a potentially important role for the enzyme in the regulation of mitochondrial biology in ischemia.Timo N. HaschlerHarry HorsleyMonika BalysGlenn AndersonJan-Willem TaanmanRobert J. UnwinJill T. NormanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Timo N. Haschler Harry Horsley Monika Balys Glenn Anderson Jan-Willem Taanman Robert J. Unwin Jill T. Norman Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
description	Abstract Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI. The mitochondrial NAD+-dependent enzyme sirtuin 5 (SIRT5) is a key regulator of mitochondrial form and function, but its role in ischemic renal injury (IRI) is unknown. SIRT5 expression was increased in murine PTECs after IRI in vivo and in human PTECs (hPTECs) exposed to an oxygen/nutrient deprivation (OND) model of IRI in vitro. SIRT5-depletion impaired ATP production, reduced mitochondrial membrane potential, and provoked mitochondrial fragmentation in hPTECs. Moreover, SIRT5 RNAi exacerbated OND-induced mitochondrial bioenergetic dysfunction and swelling, and increased degradation by mitophagy. These findings suggest SIRT5 is required for normal mitochondrial function in hPTECs and indicate a potentially important role for the enzyme in the regulation of mitochondrial biology in ischemia.
format	article
author	Timo N. Haschler Harry Horsley Monika Balys Glenn Anderson Jan-Willem Taanman Robert J. Unwin Jill T. Norman
author_facet	Timo N. Haschler Harry Horsley Monika Balys Glenn Anderson Jan-Willem Taanman Robert J. Unwin Jill T. Norman
author_sort	Timo N. Haschler
title	Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
title_short	Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
title_full	Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
title_fullStr	Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
title_full_unstemmed	Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
title_sort	sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bf7c614184604ba8a7792b2421c0cbc7
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Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells

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