Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles

The flight muscles of Drosophila are highly enriched with mitochondria, but the mechanism by which mitochondrial complex I (CI) is assembled in this tissue has not been described. We report the mechanism of CI biogenesis in Drosophila flight muscles and show that it proceeds via the formation of ∼31...

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Main Authors: Christian Joel Garcia, Jahan Khajeh, Emmanuel Coulanges, Emily I-ju Chen, Edward Owusu-Ansah
Format: Article
Language:English
Published: Elsevier 2017-07-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717308124
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author Christian Joel Garcia
Jahan Khajeh
Emmanuel Coulanges
Emily I-ju Chen
Edward Owusu-Ansah
author_facet Christian Joel Garcia
Jahan Khajeh
Emmanuel Coulanges
Emily I-ju Chen
Edward Owusu-Ansah
author_sort Christian Joel Garcia
collection DOAJ
description The flight muscles of Drosophila are highly enriched with mitochondria, but the mechanism by which mitochondrial complex I (CI) is assembled in this tissue has not been described. We report the mechanism of CI biogenesis in Drosophila flight muscles and show that it proceeds via the formation of ∼315, ∼550, and ∼815 kDa CI assembly intermediates. Additionally, we define specific roles for several CI subunits in the assembly process. In particular, we show that dNDUFS5 is required for converting an ∼700 kDa transient CI assembly intermediate into the ∼815 kDa assembly intermediate. Importantly, incorporation of dNDUFS5 into CI is necessary to stabilize or promote incorporation of dNDUFA10 into the complex. Our findings highlight the potential of studies of CI biogenesis in Drosophila to uncover the mechanism of CI assembly in vivo and establish Drosophila as a suitable model organism and resource for addressing questions relevant to CI biogenesis in humans.
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spelling doaj.art-e84b5d3bc88f4d65990bbfd09c41f9e22022-12-21T23:59:41ZengElsevierCell Reports2211-12472017-07-0120126427810.1016/j.celrep.2017.06.015Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight MusclesChristian Joel Garcia0Jahan Khajeh1Emmanuel Coulanges2Emily I-ju Chen3Edward Owusu-Ansah4Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USADepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USADepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USAProteomics Shared Resource at the Herbert Irving Comprehensive Cancer Center and Department of Pharmacology, Columbia University Medical Center, New York, NY 10032, USADepartment of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USAThe flight muscles of Drosophila are highly enriched with mitochondria, but the mechanism by which mitochondrial complex I (CI) is assembled in this tissue has not been described. We report the mechanism of CI biogenesis in Drosophila flight muscles and show that it proceeds via the formation of ∼315, ∼550, and ∼815 kDa CI assembly intermediates. Additionally, we define specific roles for several CI subunits in the assembly process. In particular, we show that dNDUFS5 is required for converting an ∼700 kDa transient CI assembly intermediate into the ∼815 kDa assembly intermediate. Importantly, incorporation of dNDUFS5 into CI is necessary to stabilize or promote incorporation of dNDUFA10 into the complex. Our findings highlight the potential of studies of CI biogenesis in Drosophila to uncover the mechanism of CI assembly in vivo and establish Drosophila as a suitable model organism and resource for addressing questions relevant to CI biogenesis in humans.http://www.sciencedirect.com/science/article/pii/S2211124717308124mitochondriacomplex I biogenesis/assemblyDrosophila
spellingShingle Christian Joel Garcia
Jahan Khajeh
Emmanuel Coulanges
Emily I-ju Chen
Edward Owusu-Ansah
Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
Cell Reports
mitochondria
complex I biogenesis/assembly
Drosophila
title Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
title_full Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
title_fullStr Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
title_full_unstemmed Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
title_short Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
title_sort regulation of mitochondrial complex i biogenesis in drosophila flight muscles
topic mitochondria
complex I biogenesis/assembly
Drosophila
url http://www.sciencedirect.com/science/article/pii/S2211124717308124
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AT emmanuelcoulanges regulationofmitochondrialcomplexibiogenesisindrosophilaflightmuscles
AT emilyijuchen regulationofmitochondrialcomplexibiogenesisindrosophilaflightmuscles
AT edwardowusuansah regulationofmitochondrialcomplexibiogenesisindrosophilaflightmuscles