Evaluation of the Mitochondrial Respiratory Chain and Oxidative Phosphorylation System Using Yeast Models of OXPHOS Deficiencies

Fontanesi, Flavia; Díaz, Francisca; Barrientos, Antoni

doi:10.1002/0471142905.hg1905s63

Cited by 14 publications

(11 citation statements)

References 59 publications

(38 reference statements)

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“…To attain this objective, we used polarography of mitochondria purified from WT and atg32Δ cells for measuring the following three kinds of respiratory rate: (i) the rate of state III (also called ADP-stimulated state) respiration [ 36 , 37 ], which was assessed immediately following addition of 50 μM ADP to mitochondria supplemented with a respiratory substrate; (ii) the rate of state IV (also known as resting, basal or ADP-independent state) respiration [ 37 , 38 ], which was monitored after the exogenously added ADP was entirely converted to ATP; and (iii) the rate of uncoupled (UC) respiration [ 37 , 39 ], which was determined after addition of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) to mitochondria incubated with a respiratory substrate in the absence of exogenous ADP. In these polarographic assays, the rates of state III, state IV and UC respiration were measured using NADH as a respiratory substrate of external NADH:quinone oxidoreductase or succinate as a respiratory substrate of complex II.…”

Section: Resultsmentioning

confidence: 99%

Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

Richard

Leonov²,

Beach³

et al. 2013

Aging

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Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how the atg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria.

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Section: Resultsmentioning

confidence: 99%

Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

Richard

Leonov²,

Beach³

et al. 2013

Aging

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show abstract

“…[ 21 ] To assess the mitochondrial function, the electron transport chain (ETC) enzyme activity of complexes I to IV was performed for mitochondria isolated from blood, heart, and brain as per the procedure of Barrientos. [ 22 ] The level of ATP was assessed immediately after isolation using the ATPlite Kit (PerkinElmer). The detailed procedures are provided in the Supporting Information Material.…”

Section: Methodsmentioning

confidence: 99%

Beneficial effect of sodium thiosulfate extends beyond myocardial tissue in isoproterenol model of infarction: Implication for nootropic effects

Ravindran

Gopalakrishnan

Kurian

2020

J Biochem & Molecular Tox

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“…A list of several such examples is provided in Table II. Several excellent reviews also provide detailed historical accounts of the role yeast have played in understanding human mitochondrial disorders (Barrientos 2003; Bassett et al 1996; Fontanesi et al 2009; Foury and Kucej 2002; Schwimmer et al 2006). …”

Section: The Yeast Saccharomyces Cerevisiaementioning

confidence: 99%

Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases

Rea

Graham

Nakamaru‐Ogiso

et al. 2010

Dev Disabil Res Revs

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The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level. Here, we review the relative utility of four different model organisms, namely the bacteria Escherichia coli, the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, in studying the role of mitochondrial proteins relevant to human disease. E. coli are single cell, prokaryotic bacteria that have proven to be a useful model system in which to investigate mitochondrial respiratory chain protein structure and function. S. cerevisiae is a single-celled eukaryote that can grow equally well by mitochondrial-dependent respiration or by ethanol fermentation, a property that has proven to be a veritable boon for investigating mitochondrial functionality. C. elegans is a multi-cellular, microscopic worm that is organized into five major tissues and has proven to be a robust model animal for in vitro and in vivo studies of primary respiratory chain dysfunction and its potential therapies in humans. Studied for over a century, D. melanogaster is a classic metazoan model system offering an abundance of genetic tools and reagents that facilitates investigations of mitochondrial biology using both forward and reverse genetics. The respective strengths and limitations of each species relative to mitochondrial studies are explored. In addition, an overview is provided of major discoveries made in mitochondrial biology in each of these four model systems.

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Evaluation of the Mitochondrial Respiratory Chain and Oxidative Phosphorylation System Using Yeast Models of OXPHOS Deficiencies

Cited by 14 publications

References 59 publications

Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

Beneficial effect of sodium thiosulfate extends beyond myocardial tissue in isoproterenol model of infarction: Implication for nootropic effects

Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases

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