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. 2022 Jul 26:9:942729.
doi: 10.3389/fmolb.2022.942729. eCollection 2022.

Nitric oxide-based regulation of metabolism: Hints from TRAP1 and SIRT3 crosstalk

Fiorella Faienza  1 , Andrea Rasola  2 , Giuseppe Filomeni  1   3   4
Affiliations

Nitric oxide-based regulation of metabolism: Hints from TRAP1 and SIRT3 crosstalk

Fiorella Faienza et al. Front Mol Biosci. .
No abstract available

Keywords: SDH; metabolism; mitochondria; nitric oxide; nitrosylation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Effect of TRAP1 and SIRT3 S-nitrosylation on SDH. Nitric oxide (NO) is generated in the mitochondria by the mitochondrial portion of NOS2 (mtNOS). Besides nitration-induced irreversible damage (not shown), it causes the S-nitrosylation of TRAP1 and SIRT3 (TRAP1-SNO and SIRT3-SNO), which are in equilibrium with low molecular weight nitrosothiols (molecules and small proteins, such as GSNO, SNO-CoA, and TrxNO), the levels of which are controlled by denitrosylases (GSNOR, SCoR, and TrxR, respectively). S-nitrosylation increases SIRT3 activity, hence promoting succinate dehydrogenase (SDH) deacetylation and activation. SIRT3 has also been reported to deacetylate and activate TRAP1, which is crucial for SIRT3 protein stability. On the other hand, S-nitrosylation inhibits TRAP1 ATPase activity and promotes its degradation via the proteasome. Being TRAP1 a negative regulator of SDH, SDH activity is consequently increased. TRAP1 S-nitrosylation may also be responsible for a shift towards a holdase-like function of the protein (as recently proposed). This additional ability of TRAP1 could alternatively affect SDH stability and activity, and may help reconcile discrepancies between different studies on the effects of SIRT3 on SDH: if it takes place or not via TRAP1 inhibition or induction.
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