Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>

Mitochondrial biogenesis is a highly controlled process that depends on diverse signalling pathways responding to cellular and environmental signals. AMP-activated protein kinase (AMPK) is a critical metabolic enzyme that acts at a central control point in cellular energy homeostasis. Numerous studi...

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Autores principales:	Malgorzata Heidorn-Czarna, Herbert-Michael Heidorn, Sanjanie Fernando, Oana Sanislav, Wieslawa Jarmuszkiewicz, Rupert Mutzel, Paul R. Fisher
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	AMP-activated protein kinase AMPK mTORC1 mitochondrial biogenesis mitochondrial phosphoproteome phosphoproteomics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2cc194ded1e64d6fba1aea8be6fb1993
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spelling	oai:doaj.org-article:2cc194ded1e64d6fba1aea8be6fb19932021-11-11T17:08:53ZChronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>10.3390/ijms2221116751422-00671661-6596https://doaj.org/article/2cc194ded1e64d6fba1aea8be6fb19932021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11675https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mitochondrial biogenesis is a highly controlled process that depends on diverse signalling pathways responding to cellular and environmental signals. AMP-activated protein kinase (AMPK) is a critical metabolic enzyme that acts at a central control point in cellular energy homeostasis. Numerous studies have revealed the crucial roles of AMPK in the regulation of mitochondrial biogenesis; however, molecular mechanisms underlying this process are still largely unknown. Previously, we have shown that, in cellular slime mould <i>Dictyostelium discoideum</i>, the overexpression of the catalytic α subunit of AMPK led to enhanced mitochondrial biogenesis, which was accompanied by reduced cell growth and aberrant development. Here, we applied mass spectrometry-based proteomics of <i>Dictyostelium</i> mitochondria to determine the impact of chronically active AMPKα on the phosphorylation state and abundance of mitochondrial proteins and to identify potential protein targets leading to the biogenesis of mitochondria. Our results demonstrate that enhanced mitochondrial biogenesis is associated with variations in the phosphorylation levels and abundance of proteins related to energy metabolism, protein synthesis, transport, inner membrane biogenesis, and cellular signalling. The observed changes are accompanied by elevated mitochondrial respiratory activity in the AMPK overexpression strain. Our work is the first study reporting on the global phosphoproteome profiling of <i>D. discoideum</i> mitochondria and its changes as a response to constitutively active AMPK. We also propose an interplay between the AMPK and mTORC1 signalling pathways in controlling the cellular growth and biogenesis of mitochondria in <i>Dictyostelium</i> as a model organism.Malgorzata Heidorn-CzarnaHerbert-Michael HeidornSanjanie FernandoOana SanislavWieslawa JarmuszkiewiczRupert MutzelPaul R. FisherMDPI AGarticleAMP-activated protein kinaseAMPKmTORC1mitochondrial biogenesismitochondrial phosphoproteomephosphoproteomicsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11675, p 11675 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AMP-activated protein kinase AMPK mTORC1 mitochondrial biogenesis mitochondrial phosphoproteome phosphoproteomics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	AMP-activated protein kinase AMPK mTORC1 mitochondrial biogenesis mitochondrial phosphoproteome phosphoproteomics Biology (General) QH301-705.5 Chemistry QD1-999 Malgorzata Heidorn-Czarna Herbert-Michael Heidorn Sanjanie Fernando Oana Sanislav Wieslawa Jarmuszkiewicz Rupert Mutzel Paul R. Fisher Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
description	Mitochondrial biogenesis is a highly controlled process that depends on diverse signalling pathways responding to cellular and environmental signals. AMP-activated protein kinase (AMPK) is a critical metabolic enzyme that acts at a central control point in cellular energy homeostasis. Numerous studies have revealed the crucial roles of AMPK in the regulation of mitochondrial biogenesis; however, molecular mechanisms underlying this process are still largely unknown. Previously, we have shown that, in cellular slime mould <i>Dictyostelium discoideum</i>, the overexpression of the catalytic α subunit of AMPK led to enhanced mitochondrial biogenesis, which was accompanied by reduced cell growth and aberrant development. Here, we applied mass spectrometry-based proteomics of <i>Dictyostelium</i> mitochondria to determine the impact of chronically active AMPKα on the phosphorylation state and abundance of mitochondrial proteins and to identify potential protein targets leading to the biogenesis of mitochondria. Our results demonstrate that enhanced mitochondrial biogenesis is associated with variations in the phosphorylation levels and abundance of proteins related to energy metabolism, protein synthesis, transport, inner membrane biogenesis, and cellular signalling. The observed changes are accompanied by elevated mitochondrial respiratory activity in the AMPK overexpression strain. Our work is the first study reporting on the global phosphoproteome profiling of <i>D. discoideum</i> mitochondria and its changes as a response to constitutively active AMPK. We also propose an interplay between the AMPK and mTORC1 signalling pathways in controlling the cellular growth and biogenesis of mitochondria in <i>Dictyostelium</i> as a model organism.
format	article
author	Malgorzata Heidorn-Czarna Herbert-Michael Heidorn Sanjanie Fernando Oana Sanislav Wieslawa Jarmuszkiewicz Rupert Mutzel Paul R. Fisher
author_facet	Malgorzata Heidorn-Czarna Herbert-Michael Heidorn Sanjanie Fernando Oana Sanislav Wieslawa Jarmuszkiewicz Rupert Mutzel Paul R. Fisher
author_sort	Malgorzata Heidorn-Czarna
title	Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
title_short	Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
title_full	Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
title_fullStr	Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
title_full_unstemmed	Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>
title_sort	chronic activation of ampk induces mitochondrial biogenesis through differential phosphorylation and abundance of mitochondrial proteins in <i>dictyostelium discoideum</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2cc194ded1e64d6fba1aea8be6fb1993
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Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>

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