Chicco 2022 Abstract Bioblast

Chicco Adam, 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. Bioblast 2022: BEC Inaugural Conference. »MitoFit Preprint«

Link: Bioblast 2022: BEC Inaugural Conference

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)

Event: Bioblast 2022

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_O2). Similarly, rotenone (a selective CI inhibitor) is utilized in the presence of NS-substrates to deduce the contribution of N-pathway flux to the total (NS-pathway) J_O2. However, under S- and some NS-pathway states, rotenone elicits a paradoxical increase in J_O2, revealing a complex interaction of N- and S-pathway substrate oxidation on J_O2 in vitro. Herein, we demonstrate inhibitory effects of >1 mM malate or malonate (a CII inhibitor) on J_O2 supported by pyruvate and/or glutamate, suggesting that endogenous succinate oxidation interacts with malate concentration to potently regulate J_O2 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

• O2k-Network Lab: US CO Fort Collins Chicco AJ

Affiliations

Chicco AJ¹, Zilhaver PT¹, Whitcomb LA¹, Fresa KJ¹, Izon CS¹, Gonzalez-Franquesa A², Dometita C³, Irving BA^3,4, Garcia-Roves PM⁵

1. Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA - [email protected]
2. NovoNordisk, Copenhagen, Denmark
3. Geisinger Obesity Institute, Danville, Pennsylvania, USA
4. Department of Kinesiology, Louisiana State University, Baton Rouge, Louisiana, USA
5. Department of Physiological Sciences, University of Barcelona, Barcelona, Spain

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