Promoter analysis of the human succinate dehydrogenase iron‐protein gene

Au, Harry C.; Scheffler, Immo E.

doi:10.1046/j.1432-1327.1998.2510164.x

Cited by 54 publications

(30 citation statements)

References 2 publications

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“…We have previously shown an induction of SIRT1 in cells and tissues under CR and stress conditions (18,19). To investigate how CR can induce a greater number of low-potential mitochondria, we determined the expression of mRNA of NRF1 and NRF2, which control the expression of nuclear genes that codify most of the subunits of mitochondrial complexes (32)(33)(34), and PPAR␣, another factor that would contribute to mitochondrial biogenesis by the activation of the fatty acid oxidation pathway (35). The expression of the respective mRNAs was determined by RT-PCR in HeLa cells incubated for 24 h with both AL and CR serum.…”

Section: Resultsmentioning

confidence: 99%

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

López-Lluch

Hunt

Jones

et al. 2006

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

617

428

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Age-related accumulation of cellular damage and death has been linked to oxidative stress. Calorie restriction (CR) is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in a variety of species. Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative stress within mitochondria remains a major focus of research. CR is hypothesized to decrease mitochondrial electron flow and proton leaks to attenuate damage caused by reactive oxygen species. We have focused our research on a related, but different, antiaging mechanism of CR. Specifically, using both in vivo and in vitro analyses, we report that CR reduces oxidative stress at the same time that it stimulates the proliferation of mitochondria through a peroxisome proliferation-activated receptor coactivator 1␣ signaling pathway. Moreover, mitochondria under CR conditions show less oxygen consumption, reduce membrane potential, and generate less reactive oxygen species than controls, but remarkably they are able to maintain their critical ATP production. In effect, CR can induce a peroxisome proliferationactivated receptor coactivator 1␣-dependent increase in mitochondria capable of efficient and balanced bioenergetics to reduce oxidative stress and attenuate age-dependent endogenous oxidative damage.aging ͉ peroxisome proliferation-activated receptor coactivator 1 ͉ reactive oxygen species O ne of the major hypotheses directing gerontological research over several decades is that aging results from the accumulation of macromolecules damaged by oxidative stress and that the major loci of this damage is the mitochondrion (1-4). This hypothesis has been proposed as one explanation of how calorie restriction (CR) in various animal models works so effectively to increase lifespan and stress resistance, reduce susceptibility to chronic disease, and attenuate age-related functional decline (5, 6). Past studies have demonstrated that CR decreases mitochondrial electron and proton leak in mammalian cells and attenuates damage resulting from intracellular oxidative stress (4, 6-9).Mitochondria provide an integrated functional network, many components of which are vulnerable to oxidative stress that can impair cellular function and increase the chance of cell death. Age-related accumulation of cellular damage and death ultimately leads to impaired organ function generating further physiological dysfunction (1, 2). The mitochondrial theory of aging proposes that somatic mutations of mtDNA induced by reactive oxygen species (ROS) are the primary cause of cellular energy decline with complex I being particularly affected by decreasing its rate of electron transport (3).CR is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in mammals and other organisms (5, 7). The mechanisms responsible for the antiaging effects of CR remain unknown and likely involve several processes. Results from many different laboratories support that both the activation of c...

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Section: Resultsmentioning

confidence: 99%

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

López-Lluch

Hunt

Jones

et al. 2006

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

617

428

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“…NRF-2 sites have been found in many other nuclear genes related to respiratory chain expression (for compilations see [26,27] including genes for Tfam [29] and the TFB isoforms where both NRF-1 and NRF-2α occupy both TFB promoters in living cells as determined by chromatin immunoprecipitation [30]. Similar control by both NRFs extend to three of the four human succinate dehydrogenase (complex II) subunit genes [54-56]. Like NRF-1, NRF-2 participates in the expression of the mitochondrial protein import machinery with functional recognition sites in TOMM70 [57,58] and TOMM20 [34] promoters.…”

Section: Nuclear Transcription Factorsmentioning

confidence: 99%

Nucleus-encoded regulators of mitochondrial function: Integration of respiratory chain expression, nutrient sensing and metabolic stress

Scarpulla¹

2012

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

138

102

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Nucleus-encoded regulatory factors are major contributors to mitochondrial biogenesis and function. Several act within the organelle to regulate mitochondrial transcription and translation while others direct the expression of nuclear genes encoding the respiratory chain and other oxidative functions. Loss-of-function studies for many of these factors reveal a wide spectrum of phenotypes. These range from embryonic lethality and severe respiratory chain deficiency to relatively mild mitochondrial defects seen only under conditions of physiological stress. The PGC-1 family of regulated coactivators (PGC-1α, PGC-1β and PRC) plays an important integrative role through their interactions with transcription factors (NRF-1, NRF-2, ERRα, CREB, YY1 and others) that control respiratory gene expression. In addition, recent evidence suggests that PGC-1 coactivators may balance the cellular response to oxidant stress by promoting a pro-oxidant environment or by orchestrating an inflammatory response to severe metabolic stress. These pathways may serve as essential links between the energy generating functions of mitochondria and the cellular REDOX environment associated with longevity, senescence and disease.

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“…There is also the potential for cross talk between the pathways, as NRF2␤ gene is also subject to regulation by NRF1 (Thompson et al 2011). NRF2-dependent promoters more than likely also contain a NRF1 binding site (Hirawake et al 1997;Au and Scheffler 1998;Elbehti-Green et al 1998). …”

Section: Nuclear Respiratory Factormentioning

confidence: 99%

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

Bremer

SniderT.

2014

Can. J. Zool.

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Modification of mitochondrial content demands the synthesis of hundreds of proteins encoded by nuclear and mitochondrial genomes. The responsibility for coordination of this process falls to nuclear-encoded master regulators of transcription. DNAbinding proteins and coactivators integrate information from energy-sensing pathways and hormones to alter mitochondrial gene expression. In mammals, the signaling cascade for mitochondrial biogenesis can be described as follows: hormonal signals and energetic information are sensed by protein-modifying enzymes that in turn regulate the post-translational modification of transcription factors. Once activated, transcription-factor complexes form on promoter elements of many of the nuclear-encoded mitochondrial genes, recruiting proteins that remodel chromatin and initiate transcription. One master regulator in mammals, PGC-1␣, is well studied because of its role in determining the metabolic phenotype of muscles, but also due to its importance in mitochondria-related metabolic diseases. However, relatively little is known about the role of this pathway in other vertebrates. These uncertainties raise broader questions about the evolutionary origins of the pathway and its role in generating the diversity in muscle metabolic phenotypes seen in nature.Résumé : La modification du contenu mitochondrial nécessite la synthèse de centaines de protéines encodées par les génomes nucléaire et mitochondrial, la coordination de ce processus étant assurée par des maîtres régulateurs de la transcription codés par le génome nucléaire. Des protéines se liant à l'ADN et des coactivateurs intègrent l'information provenant de voies de détection de l'énergie et d'hormones pour ensuite modifier l'expression des gènes mitochondriaux. Chez les mammifères, la cascade de signalisation pour la biogénèse mitochondriale peut être décrite comme suit : des enzymes de modification de protéines détectent des signaux hormonaux et de l'information énergétique et régulent la modification post-traduction des facteurs de transcription. Une fois activés, des complexes de facteurs de transcription se forment sur des éléments promoteurs de nombreux gènes mitochondriaux à encodage nucléaire, recrutant des protéines qui remodèlent la chromatine et amorcent la transcription. Un des maîtres régulateurs chez les mammifères, le PGC-1␣, fait l'objet de nombreuses études en raison de son rôle dans la détermination du phénotype métabolique des muscles, mais aussi en raison de son importance dans les maladies métaboliques associées aux mitochondries. Les connaissances sur le rôle de cette voie chez d'autres vertébrés sont toutefois limitées. Ces incertitudes soulèvent des questions plus larges concernant les origines évolutives de cette voie et son rôle dans la production de la diversité de phénotypes métaboliques musculaires observée dans la nature. [Traduit par la Rédaction]

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Promoter analysis of the human succinate dehydrogenase iron‐protein gene

Cited by 54 publications

References 2 publications

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

Nucleus-encoded regulators of mitochondrial function: Integration of respiratory chain expression, nutrient sensing and metabolic stress

Energy metabolism and cytochrome oxidase activity: linking metabolism to gene expression

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