Difference between revisions of "Chicco 2022 MitoFit"
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|title= Chicco AJ, Zilhaver PT, Whitcomb LA, Fresa KJ, Izon CS, Gonzalez-Franquesa A, Izon CS, Dometita C, Irving BA, Garcia-Roves PM (2022) Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols. MitoFit Preprints 2022.17. https://doi.org/10.26124/mitofit:2022-0017 | |title= Chicco AJ, Zilhaver PT, Whitcomb LA, Fresa KJ, Izon CS, Gonzalez-Franquesa A, Izon CS, Dometita C, Irving BA, Garcia-Roves PM (2022) Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols. MitoFit Preprints 2022.17. https://doi.org/10.26124/mitofit:2022-0017 | ||
|info=[[File:MitoFit Preprints pdf.png|left|160px|link=|MitoFit pdf]] [ Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols ]<br/> | |info=[[File:MitoFit Preprints pdf.png|left|160px|link=|MitoFit pdf]] [ Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols ]<br/> | ||
|authors=Chicco | |authors=Chicco Adam J, Zilhaver Philip T, Whitcomb Luke A, Fresa Kyle J, Izon Cheyanne S, Gonzalez-Franquesa Alba, Dometita Crystal, Irving Brian A, Garcia-Roves Pablo Miguel | ||
|year=2022-05-02 | |year=2022-05-02 | ||
|journal=MitoFit Prep | |journal=MitoFit Prep | ||
|abstract= Multi-substrate respirometry protocols are frequently used to resolve the relative contributions of NADH-producing (N-pathway or CI-linked) substrates and succinate (S-pathway or CII-linked substrate) to mitochondrial oxygen consumption rate ( | |abstract= Multi-substrate respirometry protocols are frequently used to resolve the relative contributions of NADH-producing (N-pathway or CI-linked) substrates and succinate (S-pathway or CII-linked substrate) to mitochondrial oxygen consumption rate (''J<sub>O2</sub>''). Similarly, rotenone (a selective CI inhibitor) is utilized in the presence of N+S substrates to deduce the contribution of N-pathway flux to the total (N+S-pathway) ''J<sub>O2</sub>''. However, under S- and some N+S pathway states, rotenone elicits a paradoxical increase in ''J<sub>O2</sub>'', revealing a complex interaction of N- and S-pathway substrate oxidation on ''J<sub>O2</sub>'' ''in vitro''. Herein, we demonstrate inhibitory effects of >1 mM malate or malonate (a CII inhibitor) on JO2 supported by pyruvate and/or glutamate, suggesting that endogenous succinate oxidation interacts with malate concentration to potently regulate ''J<sub>O2</sub>'' supported by N-pathway substrates in a tissue-specific manner. Potential mechanisms are discussed to stimulate further experimentation aimed at elucidating the biological bases for variations in NS-pathway flux in multi-substrate respirometry protocols. <br><br> | ||
|keywords=Mitochondrial respiration, electron transport chain, succinate, glutamate, oxidative phosphorylation, high-resolution respirometry | |keywords=Mitochondrial respiration, electron transport chain, succinate, glutamate, oxidative phosphorylation, high-resolution respirometry | ||
Revision as of 12:09, 2 May 2022
Chicco 2022 MitoFit
| Chicco AJ, Zilhaver PT, Whitcomb LA, Fresa KJ, Izon CS, Gonzalez-Franquesa A, Izon CS, Dometita C, Irving BA, Garcia-Roves PM (2022) Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols. MitoFit Preprints 2022.17. https://doi.org/10.26124/mitofit:2022-0017 |
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[ Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols ]
Chicco Adam J, Zilhaver Philip T, Whitcomb Luke A, Fresa Kyle J, Izon Cheyanne S, Gonzalez-Franquesa Alba, Dometita Crystal, Irving Brian A, Garcia-Roves Pablo Miguel (2022-05-02) MitoFit Prep
Abstract: Multi-substrate respirometry protocols are frequently used to resolve the relative contributions of NADH-producing (N-pathway or CI-linked) substrates and succinate (S-pathway or CII-linked substrate) to mitochondrial oxygen consumption rate (JO2). Similarly, rotenone (a selective CI inhibitor) is utilized in the presence of N+S substrates to deduce the contribution of N-pathway flux to the total (N+S-pathway) JO2. However, under S- and some N+S pathway states, rotenone elicits a paradoxical increase in JO2, revealing a complex interaction of N- and S-pathway substrate oxidation on JO2 in vitro. Herein, we demonstrate inhibitory effects of >1 mM malate or malonate (a CII inhibitor) on JO2 supported by pyruvate and/or glutamate, suggesting that endogenous succinate oxidation interacts with malate concentration to potently regulate JO2 supported by N-pathway substrates in a tissue-specific manner. Potential mechanisms are discussed to stimulate further experimentation aimed at elucidating the biological bases for variations in NS-pathway flux in multi-substrate respirometry protocols.
• Keywords: Mitochondrial respiration, electron transport chain, succinate, glutamate, oxidative phosphorylation, high-resolution respirometry
• Bioblast editor: Tindle-Solomon L
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