SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK.
SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK.
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DOI：
10.18632/aging.100616
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Kolthur-Seetharam U
中科院分区：
文献类型：
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作者：
Ho L;Titus AS;Banerjee KK;George S;Lin W;Deota S;Saha AK;Nakamura K;Gut P;Verdin E;Kolthur-Seetharam U
细胞能量生产与代谢需求的有效耦合对于维持生物体内平衡至关重要。在这里，我们报告说，线粒体Sirtuin Sirt 4调节线粒体ATP稳态。我们发现Sirt 4通过腺嘌呤核苷酸转运子2（ANT 2）影响线粒体解偶联。Sirt 4表达的缺失导致体外和体内细胞ATP水平降低，而Sirt 4过表达与ATP水平增加相关。此外，我们提供的证据表明，缺乏Sirt 4激活了从线粒体到细胞核的逆行信号传导反应，包括AMPK，PGC 1 α，β-氧化的关键调节因子，如乙酰辅酶A羧化酶，以及线粒体呼吸机制的组成部分。这项研究强调了Sirt 4通过ANT 2和涉及AMPK的反馈回路调节ATP水平的能力。
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 activates a retrograde signaling response from the mitochondria to the nucleus that includes AMPK, PGC1α, key regulators of β-oxidation such as Acetyl-CoA carboxylase, and components of the mitochondrial respiratory machinery. This study highlights the ability of Sirt4 to regulate ATP levels via ANT2 and a feedback loop involving AMPK.