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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1473869

Physiological relevance, localization and substrate specificity of the alternative (type II) mitochondrial NADH dehydrogenases of Ogataea parapolymorpha

Provisionally accepted
Hannes Juergens Hannes Juergens Álvaro Mielgo-Gómez Álvaro Mielgo-Gómez Albert Godoy-Hernández Albert Godoy-Hernández Jolanda Ter Horst Jolanda Ter Horst Janine M Nijenhuis Janine M Nijenhuis Duncan G. G. McMillan Duncan G. G. McMillan *Robert Mans Robert Mans
  • Delft University of Technology, Delft, Netherlands

The final, formatted version of the article will be published soon.

    Mitochondria from Ogataea parapolymorpha harbor a branched electron-transport chain containing a proton-pumping Complex I NADH dehydrogenase and three Type II NADH dehydrogenases (NDH-2). To investigate the physiological role, localization and substrate specificity of these enzymes, the growth of various NADH dehydrogenase knockout mutants was quantitatively characterized in shake-flask and chemostat cultures, followed by oxygen-uptake experiments with isolated mitochondria. NAD(P)H:quinone oxidoreduction of the three NDH-2 were individually assessed. Our findings reveal that the O. parapolymorpha respiratory chain contains an internal NADH-accepting NDH-2 (Ndh2-1/OpNdi1), at least one external NAD(P)H-accepting enzyme, and likely additional mechanisms for respiration-linked oxidation of cytosolic NADH. Metabolic regulation appears to prevent competition between OpNdi1 and Complex I for mitochondrial NADH. With the exception of OpNdi1, the respiratory chain of O. parapolymorpha exhibits metabolic redundancy and tolerates deletion of multiple NADH-dehydrogenase genes without compromising fully respiratory metabolism.

    Keywords: Mitochondria, NADH Dehydrogensase, Ogataea parapolymorpha, Bioenergetics, yeast engineering

    Received: 31 Jul 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Juergens, Mielgo-Gómez, Godoy-Hernández, Ter Horst, Nijenhuis, McMillan and Mans. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Duncan G. G. McMillan, Delft University of Technology, Delft, Netherlands

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