At one point it directly says that both fasting and calorie restricted mice display an increase in mitochondrial protein acetylation.
This must be a typo on your part. Fasting and CR decrease mitochondrial protein acetylation.
No, not a typo on my behalf. Perhaps a typo in the article I linked, but they seemed very specific about it. It could be they were being liver specific, but the last line used the word 'globally'. Hmm. Anyways, I cant CnP from the page simply, so I attached a screenshot of what I was referring to. (click on it to make it readable)
[attachment=10816:Untitled.png]
Wow. indeed but this is in complete contradiction to all the other studies. Namely, fasting upregulates SIRT3, which in turn ups mitochondrial energy production by
removing mitochondria protein acetylation.
For example, here is the quote from the metformin article
http://www.plosone.o...al.pone.0049863 : "We show that metformin downregulates SIRT3 exp<b></b>ression and that this results in increased mitochondrial protein acetylation." So, SIRT3 down = acetylation up and visa versa. Fasting ups SIRT3 => it decreases acetylation.
Or another article
http://www.ncbi.nlm....les/PMC2841477/: "We demonstrate that
increased SIRT3 expression and activity
deacetylates and enzymatically activates the fatty acid oxidation enzyme LCAD*"
"...the upregulation of SIRT3 expression and the increase in cellular NAD+ that both occur during the transition to fasting could work in synergy to maximally induce SIRT3
deacetylation of LCAD..."
*LCAD = long-chain acyl CoA dehydrogenase (aids in long-chain FA metabolism)
Or take just the title of this one: SIRT3 Deacetylates Mitochondrial 3-Hydroxy-3-Methylglutaryl CoA Synthase 2 and Regulates Ketone Body Production.
http://www.cell.com/...4131(10)00395-5Or this
http://www.cell.com/...4131(10)00395-5 :
"The mitochondrial sirtuin
SIRT3 is a mitochondrial deacetylase and is emerging as an important regulator protein acetylation and metabolic regulation during fasting. SIRT3 exp<b></b>ression is enhanced during fasting,
deacetylates long-chain acyl-CoA dehydrogenase (LCAD), and increases fatty acid oxidation in the liver (Hirschey et al., 2010). In extrahepatic tissue, SIRT3 also
deacetylates and activates mitochondrial acetylCoA synthase 2 (AceCS2) (Hallows et al., 2006 and Schwer et al., 2006), an enzyme required in the fasting response (Sakakibara et al., 2009). Additionally, SIRT3
deacetylates a subunit of the electron transport chain and regulates ATP production (Ahn et al., 2008). In this study, we identify HMGCS2 as a substrate of SIRT3, further supporting a role for SIRT3 in adaptive response to fasting."
Or this
http://www.ncbi.nlm....les/PMC3065720/ SIRT3 opposes reprogramming of cancer cell metabolism through HIF1a destabilization. 2011:
"SIRT3 is a major mitochondrial deacetylase that targets many enzymes involved in central metabolism, resulting in the activation of many oxidative pathways. For example, SIRT3 deacetylates complex I and complex II to activate electron transport. SIRT3 induces fatty acid oxidation during fasting in hepatocytes via deacetylation of LCAD. "
"SIRT3 is a mitochondrial deacetylase that activates multiple metabolic enzymes and promotes mitochondrial substrate oxidation and ATP production. Our study shows that SIRT3 additionally controls glycolytic metabolism by regulating the stability and activity of HIF1a."
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My understanding is that mitochondrial proteins are rendered inactive by acetylation. When demand for energy rises, they are deacetylated by SIRT3, which kicks mitochondria in high gear, increasing the metabolic efficiency.
LongeCity
