Mitochondrial dynamics in yeast with repressed adenine nucleotide translocator AAC2 |
| |
| Affiliation: | 1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskiye Gory 1–73, Moscow, 119991, Russia;2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskiye Gory 1–40, Moscow, 119991, Russia;3. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia;1. Department of Biology, Maynooth University, National University of Ireland, Maynooth W23F2H6, Co. Kildare, Ireland;2. Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth W23F2H6, Co. Kildare, Ireland;3. Institute of Physiology II, University of Bonn, D53115 Bonn, Germany;4. National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland;1. Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India;2. School of Biotechnology, University of Jammu, Jammu, 180006, India;3. Perelman School of Medicine, Cancer Biology Division, University of Pennsylvania, PA-19104, USA;4. Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India;5. Plant Biotechnology and System Biology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India;1. Universidad de Buenos Aires, Instituto de Oncología A.H. Roffo, Área Investigación, Buenos Aires, Argentina;2. CONICET;1. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil;2. Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil;3. Laboratório de Imunoreceptores e Sinalização, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;4. Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil;5. Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil;6. Laboratório de Biologia Celular, Departamento de Biologia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil;1. Université de Bordeaux, F-33000 Bordeaux, France;2. INSERM U1045, F-33000 Bordeaux, France;3. CBMN, UMR 5248, F-33000 Bordeaux, France;1. Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse, 76a, 123007 Moscow, Russia;2. Faculty of Basic Medicine, Moscow State University, Lomonosovsky Prospekt, 31-5, 117192, Moscow, Russia |
| |
| Abstract: | The mitochondrial network structure dynamically adapts to cellular metabolic challenges. Mitochondrial depolarisation, particularly, induces fragmentation of the network. This fragmentation may be a result of either a direct regulation of the mitochondrial fusion machinery by transmembrane potential or an indirect effect of metabolic remodelling. Activities of ATP synthase and adenine nucleotide translocator (ANT) link the mitochondrial transmembrane potential with the cytosolic NTP/NDP ratio. Given that mitochondrial fusion requires cytosolic GTP, a decrease in the NTP/NDP ratio might also account for protonophore-induced mitochondrial fragmentation. For evaluating the contributions of direct and indirect mechanisms to mitochondrial remodelling, we assessed the morphology of the mitochondrial network in yeast cells with inhibited ANT. We showed that the repression of AAC2 (PET9), a major ANT gene in yeast, increases mitochondrial transmembrane potential. However, the mitochondrial network in this strain was fragmented. Meanwhile, AAC2 repression did not prevent mitochondrial fusion in zygotes; nor did it inhibit mitochondrial hyperfusion induced by Dnm1p inhibitor mdivi-1. These results suggest that the inhibition of ANT, rather than preventing mitochondrial fusion, facilitates mitochondrial fission. The protonophores were not able to induce additional mitochondrial fragmentation in an AAC2-repressed strain and in yeast cells with inhibited ATP synthase. Importantly, treatment with the ATP synthase inhibitor oligomycin A also induced mitochondrial fragmentation and hyperpolarization. Taken together, our data suggest that ATP/ADP translocation plays a crucial role in shaping of the mitochondrial network and exemplify that an increase in mitochondrial membrane potential does not necessarily oppose mitochondrial fragmentation. |
| |
| Keywords: | Adenine nucleotide translocator AAC2 Mitochondrial dynamics Transmembrane potential Mitochondrial fusion Mitochondrial dysfunction |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
