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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2021-10-01
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:01:26Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:26Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2cc194ded1e64d6fba1aea8be6fb19932023-11-22T20:56:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211167510.3390/ijms222111675Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins in <i>Dictyostelium discoideum</i>Malgorzata Heidorn-Czarna0Herbert-Michael Heidorn1Sanjanie Fernando2Oana Sanislav3Wieslawa Jarmuszkiewicz4Rupert Mutzel5Paul R. Fisher6Department of Biology, Chemistry, Pharmacy, Institute for Biology-Microbiology, Freie Universität Berlin, 14195 Berlin, GermanyDepartment of Biology, Chemistry, Pharmacy, Institute for Biology-Microbiology, Freie Universität Berlin, 14195 Berlin, GermanyDiscipline of Microbiology, Department of Physiology, Anatomy and Microbiology, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC 3086, AustraliaDiscipline of Microbiology, Department of Physiology, Anatomy and Microbiology, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC 3086, AustraliaLaboratory of Mitochondrial Biochemistry, Department of Bioenergetics, Faculty of Biology, Adam Mickiewicz University, 61-614 Poznan, PolandDepartment of Biology, Chemistry, Pharmacy, Institute for Biology-Microbiology, Freie Universität Berlin, 14195 Berlin, GermanyDiscipline of Microbiology, Department of Physiology, Anatomy and Microbiology, School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Bundoora, VIC 3086, AustraliaMitochondrial 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.https://www.mdpi.com/1422-0067/22/21/11675AMP-activated protein kinaseAMPKmTORC1mitochondrial biogenesismitochondrial phosphoproteomephosphoproteomics |
| spellingShingle | 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> International Journal of Molecular Sciences AMP-activated protein kinase AMPK mTORC1 mitochondrial biogenesis mitochondrial phosphoproteome phosphoproteomics |
| title | 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_short | 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 |
| topic | AMP-activated protein kinase AMPK mTORC1 mitochondrial biogenesis mitochondrial phosphoproteome phosphoproteomics |
| url | https://www.mdpi.com/1422-0067/22/21/11675 |
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