Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

Nutrient limitation results in an activation of autophagy in organisms ranging from yeast, nematodes and flies to mammals. Several evolutionary conserved nutrient-sensing kinases are critical for efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cell-cycle e...

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Autores principales:	Mahsa Ebrahimi, Lukas Habernig, Filomena Broeskamp, Andreas Aufschnaiter, Jutta Diessl, Isabel Atienza, Steffen Matz, Felix A. Ruiz, Sabrina Büttner
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lifespan nutrient limitation yeast autophagy Pho85 aging Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/66272d53b3b0473b863a7fdb23b8b284
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spelling	oai:doaj.org-article:66272d53b3b0473b863a7fdb23b8b2842021-11-25T17:12:09ZPhosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway10.3390/cells101131612073-4409https://doaj.org/article/66272d53b3b0473b863a7fdb23b8b2842021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3161https://doaj.org/toc/2073-4409Nutrient limitation results in an activation of autophagy in organisms ranging from yeast, nematodes and flies to mammals. Several evolutionary conserved nutrient-sensing kinases are critical for efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cell-cycle exit and the regulation of autophagy. Here, we demonstrate that phosphate restriction results in a prominent extension of yeast lifespan that requires the coordinated activity of autophagy and the multivesicular body pathway, enabling efficient turnover of cytoplasmic and plasma membrane cargo. While the multivesicular body pathway was essential during the early days of aging, autophagy contributed to long-term survival at later days. The cyclin-dependent kinase Pho85 was critical for phosphate restriction-induced autophagy and full lifespan extension. In contrast, when cell-cycle exit was triggered by exhaustion of glucose instead of phosphate, Pho85 and its cyclin, Pho80, functioned as negative regulators of autophagy and lifespan. The storage of phosphate in form of polyphosphate was completely dispensable to in sustaining viability under phosphate restriction. Collectively, our results identify the multifunctional, nutrient-sensing kinase Pho85 as critical modulator of longevity that differentially coordinates the autophagic response to distinct kinds of starvation.Mahsa EbrahimiLukas HabernigFilomena BroeskampAndreas AufschnaiterJutta DiesslIsabel AtienzaSteffen MatzFelix A. RuizSabrina BüttnerMDPI AGarticlelifespannutrient limitationyeastautophagyPho85agingBiology (General)QH301-705.5ENCells, Vol 10, Iss 3161, p 3161 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lifespan nutrient limitation yeast autophagy Pho85 aging Biology (General) QH301-705.5
spellingShingle	lifespan nutrient limitation yeast autophagy Pho85 aging Biology (General) QH301-705.5 Mahsa Ebrahimi Lukas Habernig Filomena Broeskamp Andreas Aufschnaiter Jutta Diessl Isabel Atienza Steffen Matz Felix A. Ruiz Sabrina Büttner Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
description	Nutrient limitation results in an activation of autophagy in organisms ranging from yeast, nematodes and flies to mammals. Several evolutionary conserved nutrient-sensing kinases are critical for efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cell-cycle exit and the regulation of autophagy. Here, we demonstrate that phosphate restriction results in a prominent extension of yeast lifespan that requires the coordinated activity of autophagy and the multivesicular body pathway, enabling efficient turnover of cytoplasmic and plasma membrane cargo. While the multivesicular body pathway was essential during the early days of aging, autophagy contributed to long-term survival at later days. The cyclin-dependent kinase Pho85 was critical for phosphate restriction-induced autophagy and full lifespan extension. In contrast, when cell-cycle exit was triggered by exhaustion of glucose instead of phosphate, Pho85 and its cyclin, Pho80, functioned as negative regulators of autophagy and lifespan. The storage of phosphate in form of polyphosphate was completely dispensable to in sustaining viability under phosphate restriction. Collectively, our results identify the multifunctional, nutrient-sensing kinase Pho85 as critical modulator of longevity that differentially coordinates the autophagic response to distinct kinds of starvation.
format	article
author	Mahsa Ebrahimi Lukas Habernig Filomena Broeskamp Andreas Aufschnaiter Jutta Diessl Isabel Atienza Steffen Matz Felix A. Ruiz Sabrina Büttner
author_facet	Mahsa Ebrahimi Lukas Habernig Filomena Broeskamp Andreas Aufschnaiter Jutta Diessl Isabel Atienza Steffen Matz Felix A. Ruiz Sabrina Büttner
author_sort	Mahsa Ebrahimi
title	Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
title_short	Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
title_full	Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
title_fullStr	Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
title_full_unstemmed	Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
title_sort	phosphate restriction promotes longevity via activation of autophagy and the multivesicular body pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/66272d53b3b0473b863a7fdb23b8b284
work_keys_str_mv	AT mahsaebrahimi phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT lukashabernig phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT filomenabroeskamp phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT andreasaufschnaiter phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT juttadiessl phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT isabelatienza phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT steffenmatz phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT felixaruiz phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway AT sabrinabuttner phosphaterestrictionpromoteslongevityviaactivationofautophagyandthemultivesicularbodypathway
_version_	1718412653983956992

Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

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