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 |
»
[ Resolving the Rotenone Paradox: elucidating the complexity of multi-substrate respirometry protocols ]
Chicco AJ, Zilhaver PT, Whitcomb LA, Fresa KJ, Izon CS, Gonzalez-Franquesa A, Izon CS, Dometita C, Irving BA, Garcia-Roves PM (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: trypanosomatids, mitochondrion, bioenergetics, oxidative stress, chemotherapy
• Bioblast editor: Tindle-Solomon L
ORCID: 
Bombaça Ana Cristina S, Menna-Barreto Rubem FS
Labels: MiParea: Comparative MiP;environmental MiP Pathology: Other
Organism: Protists
Bioblast 2022, Trypanosoma
