RT journal article
T1 Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway
A1 Ebrahimi, Mahsa
A1 Habernig, Lukas
A1 Broeskamp, Filomena
A1 Aufschnaiter, Andreas
A1 Diessl, Jutta
A1 Atienza Navarro, Isabel
A1 Matz, Steffen
A1 Ruiz Rodríguez, Félix Alejandro
A1 Büttner, Sabrina
A2 BiomedicinaBiotecnología y Salud Pública
K1 lifespan
K1 nutrient limitation
K1 yeast
K1 autophagy
K1 Pho85
K1 aging
K1 polyphosphate
K1 vacuole fusion
K1 quiescence
AB 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 criticalfor efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cellcycleexit and the regulation of autophagy. Here, we demonstrate that phosphate restriction results ina prominent extension of yeast lifespan that requires the coordinated activity of autophagy and themultivesicular body pathway, enabling efficient turnover of cytoplasmic and plasma membrane cargo.While the multivesicular body pathway was essential during the early days of aging, autophagycontributed to long-term survival at later days. The cyclin-dependent kinase Pho85 was critical forphosphate restriction-induced autophagy and full lifespan extension. In contrast, when cell-cycle exitwas triggered by exhaustion of glucose instead of phosphate, Pho85 and its cyclin, Pho80, functionedas negative regulators of autophagy and lifespan. The storage of phosphate in form of polyphosphatewas completely dispensable to in sustaining viability under phosphate restriction. Collectively, ourresults identify the multifunctional, nutrient-sensing kinase Pho85 as critical modulator of longevitythat differentially coordinates the autophagic response to distinct kinds of starvation.
PB MDPI
SN 2073-4409
YR 2021
FD 2021-11
LK http://hdl.handle.net/10498/26130
UL http://hdl.handle.net/10498/26130
LA eng
NO This work was supported by the Swedish Research Council (2015-05468 and 2019-05249 to SB), the Knut and AliceWallenberg Foundation (2017.009 to SB), Stiftelsen Olle Engkvist Byggmastare (194-0681 and 207-0527 to SB), the Austrian Science Fund FWF (J4398-B to AA) and Junta de Andalucia (CTS-554 to FAR). IA was a Young Research Staff of the "Sistema de Garantia Juvenil, Fase II" (Junta de Andalucia).
DS Repositorio Institucional de la Universidad de Cádiz
RD 12-nov-2026