Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Mitochondrial sAC-cAMP-PKA Axis Modulates the ΔΨm-Dependent Control Coefficients of the Respiratory Chain Complexes: Evidence of Respirasome Plasticity

Rosella Scrima
* ,
Olga Cela
,
Michela Rosiello
,
Ari Qadir Nabi
ORCID logo ,
Claudia Piccoli
,
Giuseppe Capitanio
,
Francesco Antonio Tucci
ORCID logo ,
Aldo Leone
,
Giovanni Quarato
,
Nazzareno Capitanio
* ORCID logo
Version 1 : Received: 28 September 2023 / Approved: 29 September 2023 / Online: 30 September 2023 (08:01:36 CEST)

A peer-reviewed article of this Preprint also exists.

Scrima, R.; Cela, O.; Rosiello, M.; Nabi, A.Q.; Piccoli, C.; Capitanio, G.; Tucci, F.A.; Leone, A.; Quarato, G.; Capitanio, N. Mitochondrial sAC-cAMP-PKA Axis Modulates the ΔΨm-Dependent Control Coefficients of the Respiratory Chain Complexes: Evidence of Respirasome Plasticity. Int. J. Mol. Sci. 2023, 24, 15144. Scrima, R.; Cela, O.; Rosiello, M.; Nabi, A.Q.; Piccoli, C.; Capitanio, G.; Tucci, F.A.; Leone, A.; Quarato, G.; Capitanio, N. Mitochondrial sAC-cAMP-PKA Axis Modulates the ΔΨm-Dependent Control Coefficients of the Respiratory Chain Complexes: Evidence of Respirasome Plasticity. Int. J. Mol. Sci. 2023, 24, 15144.

Abstract

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the oc-currence of their assembly in supercomplexes providing additional functional properties as compared with randomly colliding isolated complexes. According to the plasticity model, these two structural states of the respiratory chain may interconvert influenced by the intracellular prevailing conditions and in previous studies we candidated the mitochondrial membrane po-tential as a factor controlling their dynamic balance. Here, we extended those studies investigating if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. Analysis of inhibitory-titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The results attained inhibiting pharmacologically either PKA and sAC indicate that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influences their assembly state in response to the membrane potential. This conclusion is supported by scrutiny of the available structure of the CI,CIII2,CIV respirasome enabling to map several PKA-target serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

Keywords

mitochondrial respiratory chain complexes; supercomplexes; cAMP/PKA signaling pathway; soluble adenylate cyclase; metabolic flux theory; mitochondrial membrane potential

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.