Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins

Sanz, Alberto; Caro, Pilar; Ayala, Victòria; Portero‐Otín, Manuel; Pamplona, Reinald; Barja, Gustavo

doi:10.1096/fj.05-5568com

Cited by 217 publications

(206 citation statements)

References 43 publications

(56 reference statements)

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…This supports previous evidence for the role of oxidative stress in aging (28)(29)(30)(31)(32) and contributes to a growing body of evidence suggesting that methionine abundance regulates the pathways that protect the cell from the ravages of oxidative metabolism. In higher organisms, methionine restriction has been found to increase longevity and reduce oxidative damage to proteins and mitochondrial DNA and to decrease ROS generated in the mitochondria (32).…”

Section: Role Of Mitochondrial Function and Stress Response In Starvasupporting

confidence: 88%

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Petti

Crutchfield

Rabinowitz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

103

120

View full text Add to dashboard Cite

Survival of yeast during starvation has been shown to depend on the nature of the missing nutrient(s). In general, starvation for "natural" nutrients such as sources of carbon, phosphate, nitrogen, or sulfate results in low death rates, whereas starvation for amino acids or other metabolites in auxotrophic mutants results in rapid loss of viability. Here we characterized phenotype, gene expression, and metabolite abundance during starvation for methionine. Some methionine auxotrophs (those with blocks in the biosynthetic pathway) respond to methionine starvation like yeast starving for natural nutrients such as phosphate or sulfate: they undergo a uniform cell cycle arrest, conserve glucose, and survive. In contrast, methionine auxotrophs with defects in the transcription factors Met31p and Met32p respond poorly, like other auxotrophs. We combined physiological and gene expression data from a variety of nutrient starvations (in both respiratory competent and incompetent cells) to show that successful starvation response is correlated with expression of genes encoding oxidative stress response and nonrespiratory mitochondrial functions, but not respiration per se.U nderstanding global coordination of subcellular processes during adaptation to environmental change is a central challenge in systems biology. The ability of free-living organisms to adapt to changes in their nutritional environment is clearly one of the driving forces of their evolution. In natural environments, yeast are exposed to extreme variations in "natural nutrient" availability, particularly in their sources of carbon (and energy), phosphorus, sulfur, and nitrogen. Unlike wild type strains, auxotrophic mutant yeast strains unable to make an essential metabolite (e.g., leucine or uracil) can also be starved for the missing metabolite, but adaptation to this kind of "nonnatural" starvation has not been subject to evolutionary selection. Starvation of Saccharomyces cerevisiae for a single, growth-limiting nutrient offers the opportunity to study the coordination of nutrient sensing, metabolism, growth, and cell division. Proper coordination results in prolonged survival, concerted cell cycle arrest, and glucose conservation during starvation, and depends strongly on the specific nutrient being depleted. For instance, the survival of auxotrophic yeast starved for leucine, histidine, or uracil is substantially impaired (exhibiting a roughly 10-fold difference in half-life) relative to the same strain starved for the "natural" nutrients sulfate or phosphate (1). Starvation for sulfate or phosphate elicits rapid, nearly uniform G0/G1 cell cycle arrest and slows glucose consumption, whereas starvation for leucine, histidine, or uracil results in incomplete cell cycle arrest and markedly higher rates of glucose consumption.We are interested in understanding what, if any, general principles determine starvation phenotype. Early work on nutrient starvation posited the existence of a starvation "signal" that promotes concerted cell cycle arrest and surviv...

show abstract

Section: Role Of Mitochondrial Function and Stress Response In Starvasupporting

confidence: 88%

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Petti

Crutchfield

Rabinowitz

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

103

120

View full text Add to dashboard Cite

show abstract

“…Interestingly restriction of methionine intake (40% and 80% restriction) has also been shown to decrease mitochondrial ROS generation and percent free radical leak in rat liver mitochondria (Caro et al, 2008). The same group also reported that protein restriction alone could decrease mitochondrial ROS production and mtDNA damage in rat liver (Sanz et al, 2004). Caloric restriction also retards age related diseases, studies of dietary links to Parkinson's disease and Alzheimer's suggest that individuals with a low calorie intake are at reduced risk (Matteson et al, 2002).…”

Section: Ros and Agingmentioning

confidence: 93%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

164

141

View full text Add to dashboard Cite

Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

show abstract

“…Such oxidation affects biological activity as shown by loss of ␣ 1 -antitrypsin inhibitor activity upon Met oxidation (22). Two types of methionine sulfoxide reductases act on the structurally distinct S-and R-sulfoxides (65,89,196); methionine sulfoxide reductases activities are dependent on thioredoxins (Trx) (196) and have been associated with longevity (123,130,147,152). The less common selenol of Sec undergoes reversible oxidation-reduction during catalytic functions of Trx reductases and Se-dependent GSH peroxidases (52,96).…”

Section: The Redox Hypothesismentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,032

839

View full text Add to dashboard Cite

Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

show abstract

Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins

Cited by 217 publications

References 43 publications

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Survival of starving yeast is correlated with oxidative stress response and nonrespiratory mitochondrial function

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Radical-free biology of oxidative stress

Contact Info

Product

Resources

About