Involvement of FANCD2 in Energy Metabolism via ATP5α

Abstract Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report...

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Autores principales:	Panneerselvam Jayabal, Chi Ma, Manoj Nepal, Yihang Shen, Raymond Che, James Turkson, Peiwen Fei
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46432cb0a1924c2793b56853f42e5bb1
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spelling	oai:doaj.org-article:46432cb0a1924c2793b56853f42e5bb12021-12-02T11:52:30ZInvolvement of FANCD2 in Energy Metabolism via ATP5α10.1038/s41598-017-05150-12045-2322https://doaj.org/article/46432cb0a1924c2793b56853f42e5bb12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05150-1https://doaj.org/toc/2045-2322Abstract Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report that FA complementation group D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its interaction with ATP5α, whereas this relationship was not observed in the mutant FANCD2 (K561R)-carrying cells. Moreover, while ATP5α is present within the mitochondria in wild-type cells, it is instead located mostly outside in cells that carry the non-monoubiquitinated FANCD2. In addition, mitochondrial ATP production is significantly reduced in these cells, compared to those cells carrying wtFANCD2. We identified one region (AA42-72) of ATP5α, contributing to the interaction between ATP5α and FANCD2, which was confirmed by protein docking analysis. Further, we demonstrated that mtATP5α (∆AA42-72) showed an aberrant localization, and resulted in a decreased ATP production, similar to what was observed in non-monoubiquitinated FANCD2-carrying cells. Collectively, our study demonstrates a novel role of FANCD2 in governing cellular ATP production, and advances our understanding of how defective FA signaling contributes to aging and cancer at the energy metabolism level.Panneerselvam JayabalChi MaManoj NepalYihang ShenRaymond CheJames TurksonPeiwen FeiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Panneerselvam Jayabal Chi Ma Manoj Nepal Yihang Shen Raymond Che James Turkson Peiwen Fei Involvement of FANCD2 in Energy Metabolism via ATP5α
description	Abstract Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report that FA complementation group D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its interaction with ATP5α, whereas this relationship was not observed in the mutant FANCD2 (K561R)-carrying cells. Moreover, while ATP5α is present within the mitochondria in wild-type cells, it is instead located mostly outside in cells that carry the non-monoubiquitinated FANCD2. In addition, mitochondrial ATP production is significantly reduced in these cells, compared to those cells carrying wtFANCD2. We identified one region (AA42-72) of ATP5α, contributing to the interaction between ATP5α and FANCD2, which was confirmed by protein docking analysis. Further, we demonstrated that mtATP5α (∆AA42-72) showed an aberrant localization, and resulted in a decreased ATP production, similar to what was observed in non-monoubiquitinated FANCD2-carrying cells. Collectively, our study demonstrates a novel role of FANCD2 in governing cellular ATP production, and advances our understanding of how defective FA signaling contributes to aging and cancer at the energy metabolism level.
format	article
author	Panneerselvam Jayabal Chi Ma Manoj Nepal Yihang Shen Raymond Che James Turkson Peiwen Fei
author_facet	Panneerselvam Jayabal Chi Ma Manoj Nepal Yihang Shen Raymond Che James Turkson Peiwen Fei
author_sort	Panneerselvam Jayabal
title	Involvement of FANCD2 in Energy Metabolism via ATP5α
title_short	Involvement of FANCD2 in Energy Metabolism via ATP5α
title_full	Involvement of FANCD2 in Energy Metabolism via ATP5α
title_fullStr	Involvement of FANCD2 in Energy Metabolism via ATP5α
title_full_unstemmed	Involvement of FANCD2 in Energy Metabolism via ATP5α
title_sort	involvement of fancd2 in energy metabolism via atp5α
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/46432cb0a1924c2793b56853f42e5bb1
work_keys_str_mv	AT panneerselvamjayabal involvementoffancd2inenergymetabolismviaatp5a AT chima involvementoffancd2inenergymetabolismviaatp5a AT manojnepal involvementoffancd2inenergymetabolismviaatp5a AT yihangshen involvementoffancd2inenergymetabolismviaatp5a AT raymondche involvementoffancd2inenergymetabolismviaatp5a AT jamesturkson involvementoffancd2inenergymetabolismviaatp5a AT peiwenfei involvementoffancd2inenergymetabolismviaatp5a
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Involvement of FANCD2 in Energy Metabolism via ATP5α

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