2013
DOI: 10.18632/aging.100616
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Abstract: Efficient coupling of cellular energy production to metabolic demand is crucial to maintain organismal homeostasis. Here, we report that the mitochondrial Sirtuin Sirt4 regulates mitochondrial ATP homeostasis. We find that Sirt4 affects mitochondrial uncoupling via the adenine nucleotide translocator 2 (ANT2). Loss of Sirt4 expression leads to decreased cellular ATP levels in vitro and in vivo while Sirt4 overexpression is associated with increased ATP levels. Further, we provide evidence that lack of Sirt4 ac… Show more

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Cited by 117 publications
(151 citation statements)
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References 42 publications
(92 reference statements)
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“…B-lymphocyte development might require more oxidative respiration, while T-cell development may be more dependent on glycolytic energy metabolism. Alternatively, Ant2-interacting proteins such as Sirt4 26 and Btg2 27 could be differentially expressed or regulated in these cell populations. The roles of such proteins in Ant2 depletion-mediated cell death would be interesting subjects to explore.…”
Section: Discussionmentioning
confidence: 99%
“…Similar observations were recently also reported for human cells deficient in SIRT4. Knockdown of SIRT4 in Human Embryonic Kidney 293 cells resulted in increased ADP/ ATP ratios, while overexpression of SIRT4 showed the opposite effect (Ho et al, 2013). Furthermore, Ho et al (2013) demonstrated that the activity of the mitochondrial ATP synthase was not affected by the loss of SIRT4 but that uncoupling of mitochondria was increased.…”
Section: Srt2 Interacts With Proteins Of the Inner Mitochondrial Membmentioning
confidence: 98%
“…Knockdown of SIRT4 in Human Embryonic Kidney 293 cells resulted in increased ADP/ ATP ratios, while overexpression of SIRT4 showed the opposite effect (Ho et al, 2013). Furthermore, Ho et al (2013) demonstrated that the activity of the mitochondrial ATP synthase was not affected by the loss of SIRT4 but that uncoupling of mitochondria was increased. Interestingly, uncoupling of respiration was relieved when the ATP/ADP carrier ADP/ATP Translocase2 was knocked down simultaneously with SIRT4 (Ho et al, 2013).…”
Section: Srt2 Interacts With Proteins Of the Inner Mitochondrial Membmentioning
confidence: 98%
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“…Sirtuins are also energy sensor proteins that respond Experimental Gerontology 79 (2016) [46][47][48][49][50][51][52][53][54] strongly to caloric restriction, a well-recognized intervention to increase life span of lower model organisms and rodents as well as primates Bodkin et al, 2003). Furthermore, sirtuins play a role in the selection of energy source by regulating fatty acid oxidation Nasrin et al, 2010) along with mitochondrial energy metabolism and ATP homeostasis (Ho et al, 2013;Park et al, 2013).…”
Section: Introductionmentioning
confidence: 99%