The Phosphorylation Status of Hsp82 Regulates Mitochondrial Homeostasis During Glucose Sensing in Saccharomyces cerevisiae |
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| Affiliation: | 1. IDIBE, Universidad Miguel Hernández, 03202 Elche (Alicante), Spain;2. Centro de Biotecnología, Universidad Nacional de Loja, Avda. Pío Jaramillo Alvarado s/n, Loja, 110111 Loja, Ecuador;3. Institute of Biocomputation and Physics of Complex Systems – Joint Unit GBsC-CSIC-BIFI, Universidad de Zaragoza, 50018 Zaragoza, Spain;4. CNR-NANOTEC, SS Rende (CS), Department of Physics, University of Calabria, 87036 Rende, Italy;5. Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l''Almazara 11, 03203 Elche (Alicante), Spain;6. Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France;1. Forschungszentrum Jülich, Structural Biochemistry (IBI-7) and Jülich Center for Structural Biology (JuStruct), Wilhelm-Johnen-Straße, 52425 Jülich, Germany;2. Heinrich Heine University of Düsseldorf, Physical Biology, Universitätsstraße 1, 40225 Düsseldorf, Germany;3. Max-Planck Institute for Multidisciplinary Sciences, Dept. of Neurobiology, Am Faßberg 11, 37077 Göttingen, Germany;4. Jülich Centre for Neutron Science (JCNS-1) and Institute for Biological Information Processing (IBI-8), Forschungszentrum Jülich GmbH, 52428 Jülich, Germany;5. Dept. of Physical Chemistry, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain;1. Monash University, Melbourne, Australia;2. Center for Inflammation and Tolerance; Cincinnati Children’s Hospital, Cincinnati, USA;3. U. Libre Brussels, Brussels, Belgium;4. Stanford University School of Medicine, Stanford, CA, USA;5. Southern Denmark University, Copenhagen, Denmark;6. Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg, Hamburg, Germany;7. Telethon Kids Institute, Perth, WA, Australia;1. Agharkar Research Institute, Nanobioscience Group, G. G. Agarkar Road, Pune 411004, India;2. Savitribai Phule Pune University, Ganeshkhind, Pune 411 007, India |
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| Abstract: | Sensing extracellular glucose, budding yeast switches from aerobic glycolysis to oxidative phosphorylation to adapt to environmental changes. During the conversion of metabolic mode, mitochondrial function and morphology change significantly. Mitochondria are the main supply factories of energy for various life activities in cells. However, the research on the signal pathways from glucose sensing to changes in mitochondrial function and morphology is still scarce and worthy of further exploration. In this study, we found that in addition to the known involvement of molecular chaperone Hsp82 in stress response during the conversion of metabolic mode, the phosphorylation status of Hsp82 at S485 residue regulates mitochondrial function and morphology to maintain mitochondrial homeostasis. The Hsp82S485A mutant that mimics dephosphorylation at S485 residue showed abnormal growth phenotypes related to mitochondrial defects, such as the petite phenotype, slow growth rates, and inability to use non-fermentable carbon sources. Further exploring the causes of growth defects, we found that the Hsp82S485A mutant caused mitochondrial dysfunction, including a decrease in cellular oxygen consumption rate, defects in mitochondrial electron transport chain, decreased mitochondrial membrane potential and complete loss of mtDNA. Furthermore, the Hsp82S485A mutant displayed fragmented or globular mitochondria, which may be responsible for its mitochondrial dysfunction. Our findings suggested that the phosphorylation status of Hsp82 at S485 residue might regulate mitochondrial function and morphology by affecting the stability of mitochondrial fission and fusion-related proteins. Thus, Hsp82 might be a key molecule in the signal pathway from glucose sensing to changes in mitochondrial function and morphology. |
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| Keywords: | Hsp82 phosphorylation glucose sensing mitochondrial function mitochondrial morphology |
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