Mitophagy in Yeast: Molecular Mechanism and Regulation

Innokentev, Aleksei; Kanki, Tomotake

doi:10.3390/cells10123569

Cited by 17 publications

(9 citation statements)

References 73 publications

(92 reference statements)

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“…Octanoic acid is suggested to cause oxidative damage to the yeast cell [ 19 ] triggering cellular responses involving mitochondria to counteract these perturbations. The first response involves, mitophagy, contributing to mitochondrial homeostasis by preventing the production of excessive ROS [ 78 ]. Mitophagy, defined as the degradation of damaged mitochondria [ 79 ] was also suggested in our study to play an important role in octanoic acid stress tolerance.…”

Section: Discussionmentioning

confidence: 99%

Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids

Mota,

Matos,

Bahri

et al. 2024

Microb Cell Fact

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Background The improvement of yeast tolerance to acetic, butyric, and octanoic acids is an important step for the implementation of economically and technologically sustainable bioprocesses for the bioconversion of renewable biomass resources and wastes. To guide genome engineering of promising yeast cell factories toward highly robust superior strains, it is instrumental to identify molecular targets and understand the mechanisms underlying tolerance to those monocarboxylic fatty acids. A chemogenomic analysis was performed, complemented with physiological studies, to unveil genetic tolerance determinants in the model yeast and cell factory Saccharomyces cerevisiae exposed to equivalent moderate inhibitory concentrations of acetic, butyric, or octanoic acids. Results Results indicate the existence of multiple shared genetic determinants and pathways underlying tolerance to these short- and medium-chain fatty acids, such as vacuolar acidification, intracellular trafficking, autophagy, and protein synthesis. The number of tolerance genes identified increased with the linear chain length and the datasets for butyric and octanoic acids include the highest number of genes in common suggesting the existence of more similar toxicity and tolerance mechanisms. Results of this analysis, at the systems level, point to a more marked deleterious effect of an equivalent inhibitory concentration of the more lipophilic octanoic acid, followed by butyric acid, on the cell envelope and on cellular membranes function and lipid remodeling. The importance of mitochondrial genome maintenance and functional mitochondria to obtain ATP for energy-dependent detoxification processes also emerged from this chemogenomic analysis, especially for octanoic acid. Conclusions This study provides new biological knowledge of interest to gain further mechanistic insights into toxicity and tolerance to linear-chain monocarboxylic acids of increasing liposolubility and reports the first lists of tolerance genes, at the genome scale, for butyric and octanoic acids. These genes and biological functions are potential targets for synthetic biology approaches applied to promising yeast cell factories, toward more robust superior strains, a highly desirable phenotype to increase the economic viability of bioprocesses based on mixtures of volatiles/medium-chain fatty acids derived from low-cost biodegradable substrates or lignocellulose hydrolysates.

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Section: Discussionmentioning

confidence: 99%

Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids

Mota,

Matos,

Bahri

et al. 2024

Microb Cell Fact

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“…Mitophagy is a selective type of autophagy that targets damaged mitochondria for degradation in vacuoles. Along with mitochondrial dynamics, mitophagy is of central importance to the sustainment of mitochondrial integrity and activity [93][94][95][96]. This led us to investigate whether Vps27 is involved in the modulation of mitophagy and mitochondrial biogenesis in cells lacking Sit4.…”

Section: Vps27 Is Crucial For Mitochondrial Function In Sit4∆ Cellsmentioning

confidence: 99%

Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae

Martins,

Correia,

Pinheiro

et al. 2024

Cells

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The Sit4 protein phosphatase plays a key role in orchestrating various cellular processes essential for maintaining cell viability during aging. We have previously shown that SIT4 deletion promotes vacuolar acidification, mitochondrial derepression, and oxidative stress resistance, increasing yeast chronological lifespan. In this study, we performed a proteomic analysis of isolated vacuoles and yeast genetic interaction analysis to unravel how Sit4 influences vacuolar and mitochondrial function. By employing high-resolution mass spectrometry, we show that sit4Δ vacuolar membranes were enriched in Vps27 and Hse1, two proteins that are part of the endosomal sorting complex required for transport-0. In addition, SIT4 exhibited a negative genetic interaction with VPS27, as sit4∆vps27∆ double mutants had a shortened lifespan compared to sit4∆ and vps27∆ single mutants. Our results also show that Vps27 did not increase sit4∆ lifespan by improving protein trafficking or vacuolar sorting pathways. However, Vps27 was critical for iron homeostasis and mitochondrial function in sit4∆ cells, as sit4∆vps27∆ double mutants exhibited high iron levels and impaired mitochondrial respiration. These findings show, for the first time, cross-talk between Sit4 and Vps27, providing new insights into the mechanisms governing chronological lifespan.

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“…Among these, there is an interaction between the C-terminal and N-terminal amino acid residues of Atg11 and Atg32. Atg32 is then recruited into the vacuoles alongside mitochondria, where mitochondria are degraded by vacuolar hydrolases [ 19 ].…”

Section: Types Of Selective Autophagy and Their Mechanismsmentioning

confidence: 99%

Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives

Liu,

Wu,

Meng

et al. 2024

Mol Cancer

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Eukaryotic cells engage in autophagy, an internal process of self-degradation through lysosomes. Autophagy can be classified as selective or non-selective depending on the way it chooses to degrade substrates. During the process of selective autophagy, damaged and/or redundant organelles like mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes, and lipid droplets are selectively recycled. Specific cargo is delivered to autophagosomes by specific receptors, isolated and engulfed. Selective autophagy dysfunction is closely linked with cancers, neurodegenerative diseases, metabolic disorders, heart failure, etc. Through reviewing latest research, this review summarized molecular markers and important signaling pathways for selective autophagy, and its significant role in cancers. Moreover, we conducted a comprehensive analysis of small-molecule compounds targeting selective autophagy for their potential application in anti-tumor therapy, elucidating the underlying mechanisms involved. This review aims to supply important scientific references and development directions for the biological mechanisms and drug discovery of anti-tumor targeting selective autophagy in the future.

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Mitophagy in Yeast: Molecular Mechanism and Regulation

Cited by 17 publications

References 73 publications

Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids

Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids

Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae

Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives

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