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Difference between revisions of "Chicco 2022 Abstract Bioblast"

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[[File:Bioblast2022 banner.jpg|link=Bioblast_2022]]
{{Abstract
{{Abstract
|title=[[File:Chicco Headshot.jpg|left|100px|Chicco Adam]] <u>Chicco Adam</u>, 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. <br>[[Chicco 2022 MitoFit|»''MitoFit Preprint''«]]  
|title=[[File:Chicco Headshot.jpg|left|100px|Chicco Adam]] <u>Chicco Adam</u>, 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. <br>[[Chicco 2022 MitoFit|»''MitoFit Preprint''«]]  
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|year=2022
|year=2022
|event=[[Bioblast 2022]]
|event=[[Bioblast 2022]]
|abstract=
|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>O<sub>2</sub></sub>). 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''<sub>O<sub>2</sub></sub>. However, under S- and some NS-pathway states, rotenone elicits a paradoxical increase in ''J''<sub>O<sub>2</sub></sub>, revealing a complex interaction of N- and S-pathway substrate oxidation on ''J''<sub>O<sub>2</sub></sub> ''in vitro''. Herein, we demonstrate inhibitory effects of >1 mM malate or malonate (a CII inhibitor) on ''J''<sub>O<sub>2</sub></sub> supported by pyruvate and/or glutamate, suggesting that endogenous succinate oxidation interacts with malate concentration to potently regulate ''J''<sub>O<sub>2</sub></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.
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
|mipnetlab=US CO Fort Collins Chicco AJ
|mipnetlab=US CO Fort Collins Chicco AJ
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== Affiliations ==
== Affiliations ==
:::: Chicco AJ(1), Zilhaver PT(1), Whitcomb LA(1), Fresa KJ(1), Izon CS(1), Gonzalez-Franquesa A(2), Dometita C(3), Irving BA(3,4), Garcia-Roves PM(5)
:::: Chicco AJ<sup>1</sup>, Zilhaver PT<sup>1</sup>, Whitcomb LA<sup>1</sup>, Fresa KJ<sup>1</sup>, Izon CS<sup>1</sup>, Gonzalez-Franquesa A<sup>2</sup>, Dometita C<sup>3</sup>, Irving BA<sup>3,4</sup>, Garcia-Roves PM<sup>5</sup>
 
::::#Department of Biomedical Sciences, Colorado State  University, Fort Collins, Colorado, USA - [email protected]
::::#NovoNordisk, Copenhagen, Denmark
::::#Geisinger Obesity Institute, Danville, Pennsylvania, USA
::::#Department of Kinesiology, Louisiana State University, Baton Rouge, Louisiana, USA
::::#Department of Physiological Sciences, University of Barcelona, Barcelona, Spain
 


::::# Department of Biomedical Sciences, Colorado State  University, Fort Collins, Colorado, USA - [email protected]
::::# NovoNordisk, Copenhagen, Denmark
::::# Geisinger Obesity Institute, Danville, Pennsylvania, USA
::::# Department of Kinesiology, Louisiana State University, Baton Rouge, Louisiana, USA
::::# Department of Physiological Sciences, University of Barcelona, Barcelona, Spain


== Help ==
== Help ==

Revision as of 14:03, 22 May 2022

Bioblast2022 banner.jpg

Chicco Adam
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 (JO2). 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) JO2. However, under S- and some NS-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

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 BA3,4, 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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