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Nitric oxide acts as a unifying molecular switch to trigger the whole mitochondrial biogenesis process.

nad mitochondrial biogenesis

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#1 Phoebus

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Posted 13 September 2018 - 03:08 PM


Fascinating Study here on how NO is so critical for mitochondrial biogenesis 

 

 

Nitric oxide and mitochondrial biogenesis

Enzo NisoliMichele O. Carruba
J Cell Sci 2006 119: 2855-2862; doi: 10.1242/jcs.03062

 

 

Summary

 

The characteristic structural organization of mitochondria is the product of synthesis of macromolecules within the mitochondria together with the import of proteins and lipids synthesized outside the organelle. Synthetic and import processes are required for mitochondrial proliferation and might also facilitate the growth of pre-existing mitochondria. Recent evidence indicates that these events are regulated in a complex way by several agonists and environmental conditions, through activation of specific signaling pathways and transcription factors. A newly discovered role of this organelle in retrograde intracellular signaling back to the nucleus has also emerged. This is likely to have far-reaching implications in development, aging, disease and environmental adaptation.

 

Generation of nitric oxide (NO) appears to be an important player in these processes, possibly acting as a unifying molecular switch to trigger the whole mitochondrial biogenesis process. High levels of NO acutely inhibit cell respiration by binding to cytochrome c oxidase. Conversely, chronic, smaller increases in NO levels stimulate mitochondrial biogenesis in diverse cell types. NO-induced mitochondrial biogenesis seems to be linked to proliferation and differentiation of normal and tumor cells, as well as in aging.

 

http://jcs.biologist...ent/119/14/2855

 

 

If I am reading this right, high levels of NO are bad, but chronic low levels of NO stimulate  mitochondrial biogenesis

 

full study at link 


Edited by Phoebus, 13 September 2018 - 03:08 PM.

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#2 Heisok

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Posted 13 September 2018 - 03:32 PM

Very detailed discussion. I could be wrong, but I read it a little differently. Not low levels, but long term, smaller increases from existing levels. What magnitude of actual increases is the question.

 

"High levels of NO acutely inhibit cell respiration by binding to cytochrome c oxidase. Conversely, chronic, smaller increases in NO levels stimulate mitochondrial biogenesis in diverse cell types. NO-induced mitochondrial biogenesis seems to be linked to proliferation and differentiation of normal and tumor cells, as well as in aging." 

 

“If we wish to live longer and, then, to rid ourselves of the diseases of old age, we will need more mitochondria”, writes Nick Lane in his book (Lane, 2005). In principle, this could be achieved pharmacologically, with NO donors for example. Such an approach would have the potential to cure all diseases of old age at once, rather than trying to tackle each independently, a tack that has so far failed to deliver meaningful clinical breakthroughs.

 

"Perspectives

 

Mitochondria are important dynamic organelles for cell survival and function. Their biogenesis might be involved in the control of cell metabolism and signal transduction, and requires the choreographed expression of diverse transcription activators, including PGC-1α and NRF-1. We now know that NO acts as a key messenger to activate the mitochondrial biogenesis program in various cell types. However, many issues remain to be elucidated. These include: (1) the precise mechanism(s) by which NO activates PGC-1α and/or NRF-1 to trigger mitochondrial biogenesis; (2) the nature of its effects on mitochondrial dynamics; (3) the relationship between mitochondrial NO and cytosolic and/or nuclear NO in the modulation of gene expression in the nucleus; (4) the links between NO, mitochondrial biogenesis and apoptosis; and (5) the true relevance of NO-induced mitochondrial biogenesis for prevention of aging-related diseases. Future research on the role of NO in mitochondrial biology will give us important insights into the evolution of eukaryotic life and, perhaps, the treatment of multiple diseases."

 


Edited by Heisok, 13 September 2018 - 03:33 PM.

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#3 Phoebus

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Posted 13 September 2018 - 03:37 PM

NO also seems to be critical aspect of calorie Restriction (CR) affect on longevity 

 

 

 

Recent evidence indicates that CR induces eNOS and that the resulting surge of NO activates synthesis of a broad array of mitochondrial proteins and increases production of mtDNA, respiration and ATP levels in several different tissues and organs, including white and brown fat, brain, liver and heart (Nisoli et al., 2005). Intriguingly, NO also activates expression of the mammalian Sir2 ortholog SIRT1, which is induced in mouse tissues by CR in wild-type mice but not in eNOS–/– mice (Nisoli et al., 2005). Because SIRT1 is known to mediate resistance to cellular stress by a variety of mechanisms (Luo et al., 2001), increases in its levels might be essential for greater longevity of the organism. These findings lead to a model in which CR induces eNOS, which results in mitochondrial biogenesis through increased PGC-1α expression and upregulation of SIRT1 and perhaps other longevity-promoting agents (Fig. 2). Preliminary results suggest that SIRT1 mediates mitochondrial biogenesis in fat cells by increasing PGC-1α expression (E.N., C. Tonello and M.O.C., unpublished results) and, recently, López-Lluch et al. confirmed that CR induces mitochondrial biogenesis and bioenergetic efficiency both in vitro and in vivo (López-Lluch et al., 2006).

 

 

and then goes on to speculate about a pharma based NO donor type of anti aging medication 

 

 

 

“If we wish to live longer and, then, to rid ourselves of the diseases of old age, we will need more mitochondria”, writes Nick Lane in his book (Lane, 2005). In principle, this could be achieved pharmacologically, with NO donors for example. Such an approach would have the potential to cure all diseases of old age at once, rather than trying to tackle each independently, a tack that has so far failed to deliver meaningful clinical breakthroughs.

 


Edited by Phoebus, 13 September 2018 - 03:44 PM.

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#4 Phoebus

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Posted 13 September 2018 - 03:59 PM

 

 

The influence of NO on mitochondrial respiratory chain can be summarized as follow: (a) NO inhibits cytochrome c oxidase activity by competing with oxygen; (b) NO inhibits electron transfer between cytochrome b and c and increases mitochondrial production of O2; and © NO inhibits electron transfer and NADH-dehydrogenase function in Complex I [3].

https://www.ncbi.nlm...les/PMC3546744/







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