| Autor: |
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 M |
| Rok vydání: |
2022 |
| DOI: |
10.26124/mitofit:2022-0017 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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