Interorganelle Signaling Is a Determinant of Longevity in Saccharomyces cerevisiae

Kirchman, Paul A.; Kim, Sang-Kyu; Lai, Chi Yung; Jazwinski, S. Michal

doi:10.1093/genetics/152.1.179

Cited by 300 publications

(30 citation statements)

References 69 publications

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“…The RTG pathway is the most thoroughly-understood pathway for mitochondria-to-nucleus signaling upon mitochondrial dysfunction. This retrograde pathway is activated upon mtDNA loss, and is thereby a prime candidate for mediating the signaling that leads to the G1- to-S transition delay in mtDNA-depleted cells (Liao and Butow, 1993; Kirchman et al, 1999). We first tested the effect of deleting the gene encoding the proximal sensor of the RTG pathway, RTG2 .…”

Section: Resultsmentioning

confidence: 99%

“…The RTG-dependent retrograde signaling pathway is not required for the G1-to-S phase delay in ρ 0 cells The RTG pathway is the most thoroughly-understood pathway for mitochondria-tonucleus signaling upon mitochondrial dysfunction. This retrograde pathway is activated upon mtDNA loss, and is thereby a prime candidate for mediating the signaling that leads to the G1to-S transition delay in mtDNA-depleted cells (Liao and Butow, 1993;Kirchman et al, 1999).…”

Section: The G1-s Delay In ρ 0 Cells Is Not Dependent On Central Chec...mentioning

confidence: 99%

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Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression

Gorospe

Curbelo

Carvalho

et al. 2022

Preprint

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Mitochondria are central to numerous anabolic and catabolic pathways whereby mitochondrial dysfunction has a profound impact on metabolism and can manifest in disease. The consequences of mitochondrial dysfunction can be ameliorated by adaptive responses that rely on mito-cellular crosstalk to communicate mitochondrial distress to the rest of the cell. Such mito-cellular signaling slows cell cycle progression in mitochondrial-DNA deficient (ρ0) Saccharomyces cerevisiae cells, but the initial trigger and the pathway mediating the response has remained unknown. Here, we show that decreased mitochondrial membrane potential (ΔΨm) acts as the initial signal of mitochondrial stress that delays G1-to-S phase transition in both ρ0 and control cells. Accordingly, experimentally increasing ΔΨm was sufficient to restore timely cell cycle progression in ρ0 cells. Neither the RTG retrograde pathway nor central DNA damage checkpoint kinases were involved in mediating this form of mito-cellular communication. The identification of ΔΨm as a novel regulator of cell cycle progression may have implications for disease states involving mitochondrial dysfunction.

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Section: Resultsmentioning

confidence: 99%

Section: The G1-s Delay In ρ 0 Cells Is Not Dependent On Central Chec...mentioning

confidence: 99%

Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression

Gorospe

Curbelo

Carvalho

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…In this paper, we only focused on ROS production by mitochondria. Jazwinski and co-workers identified that mitochondrial dysfunction triggers a retrograde response, which is beneficial for lifespan extension (Kirchman et al, 1999;Jazwinsk 2005). Moreover, moderate ROS stimulation enhances autophagy, a vacuolar process that degrades damaged proteins and organelles (Scherz-Shouval and Elazar 2007).…”

Section: Discussionmentioning

confidence: 99%

An Age-dependent Feedback Control Model for Calcium and Reactive Oxygen Species in Yeast Cells

Liu¹

2022

Preprint

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Calcium and reactive oxygen species (ROS) interact with each other and play an important role in cell signaling networks. Based on the existing mathematical models, we develop an age-dependent feedback control model to simulate the interaction. The model consists of three subsystems: cytosolic calcium dynamics, ROS generation from the respiratory chain in mitochondria, and mitochondrial energy metabolism. In the model, we hypothesized that ROS induces calcium release from the yeast endoplasmic reticulum , Golgi apparatus, and vacuoles, and that ROS damages calmodulin and calcineurin by oxidizing them. The dependence of calcium uptake by Vcx1p on ATP is incorporated into the model. The model can approximately reproduce the log phase calcium dynamics. The simulated interaction between the cytosolic calcium and mitochondrial ROS shows that an increase in calcium results in a decrease in ROS initially (in log phase), but the increase-decrease relation is changed to an increase-increase relation when the cell is getting old. This could accord with the experimental observation that calcium diminishes ROS from complexes I and III of the respiratory chain under normal conditions, but enhances ROS when the complex formations are inhibited. The model predicts that the subsystem of the calcium regulators Pmc1p, Pmr1p, and Vex1p is stable, controllable, and observable. These structural properties of the dynamical system could mathematically confirm that cells have evolved delicate feedback control mechanisms to maintain their calcium homeostasis.

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“…, 2015 ). Retrograde signaling is also connected to the Ras/PKA and TORC1 pathways ( Matsuura and Anraku, 1993 ; Kirchman et al. , 1999 ; Liu et al.…”

Section: Discussionmentioning

confidence: 99%

Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants

Lewis

Caldwell

Rogers

et al. 2021

MBoC

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The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear if these phenotypes directly cause the suppression or are simply effects. This work further highlights the complex cellular network connections between metabolic pathways and signaling events in the cell, and their potential roles in aging and age-related diseases.

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Interorganelle Signaling Is a Determinant of Longevity in Saccharomyces cerevisiae

Cited by 300 publications

References 69 publications

Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression

Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression

An Age-dependent Feedback Control Model for Calcium and Reactive Oxygen Species in Yeast Cells

Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants

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