Mitochondrial sAC-cAMP-PKA Axis Modulates the m-Dependent Control Coefficients of the Respiratory Chain Complexes: Evidence of Respirasome Plasticity
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..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Preprints.org - (2023) vom: 01. Okt. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Scrima, Rosella [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.20944/preprints202309.2144.v1 |
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| PPN (Katalog-ID): |
preprintsorg041024915 |
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| 520 | |a 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. | ||
| 700 | 1 | |a Cela, Olga |4 aut | |
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