Ho, Linh ; Titus, Allen Sam ; Banerjee, Kushal Kr ; George, Suji ; Lin, Wei ; Deota, Shaunak ; Saha, Asish K. ; Nakamura, Ken ; Gut, Philipp ; Verdin, Eric ; Kolthur-Seetharam, Ullas (2013) SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK Aging, 5 (11). pp. 835-849. ISSN 1945-4589
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Official URL: http://doi.org/10.18632/aging.100616
Related URL: http://dx.doi.org/10.18632/aging.100616
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 levelsin 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.
Item Type: | Article |
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Source: | Copyright of this article belongs to Impact Journals, LLC. |
Keywords: | Sirt4; ANT2; AMPK; ATP; Mitochondrial Signaling. |
ID Code: | 118216 |
Deposited On: | 19 May 2021 07:49 |
Last Modified: | 19 May 2021 07:49 |
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