دورية أكاديمية
High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts
| العنوان: | High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts |
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| المؤلفون: | Godtliebsen, Gustav, Larsen, Kenneth Bowitz, Bhujabal, Zambarlal Babanrao, Opstad, Ida Sundvor, Nager Grifo, Mireia, Punnakkal, Abhinanda Ranjit, Kalstad, Trine, Olsen, Randi, Lund, trine, Prasad, Dilip K., Agarwal, Krishna, Myrmel, Truls, Birgisdottir, Åsa birna |
| بيانات النشر: | Taylor & Francis |
| سنة النشر: | 2023 |
| المجموعة: | University of Tromsø: Munin Open Research Archive |
| الوصف: | Mitochondria are susceptible to damage resulting from their activity as energy providers. Damaged mitochondria can cause harm to the cell and thus mitochondria are subjected to elaborate quality-control mechanisms including elimination via lysosomal degradation in a process termed mitophagy. Basal mitophagy is a house-keeping mechanism fine-tuning the number of mitochondria according to the metabolic state of the cell. However, the molecular mechanisms underlying basal mitophagy remain largely elusive. In this study, we visualized and assessed the level of mitophagy in H9c2 cardiomyoblasts at basal conditions and after OXPHOS induction by galactose adaptation. We used cells with a stable expression of a pH-sensitive fluorescent mitochondrial reporter and applied state-of-the-art imaging techniques and image analysis. Our data showed a significant increase in acidic mitochondria after galactose adaptation. Using a machine-learning approach we also demonstrated increased mitochondrial fragmentation by OXPHOS induction. Furthermore, super-resolution microscopy of live cells enabled capturing of mitochondrial fragments within lysosomes as well as dynamic transfer of mitochondrial contents to lysosomes. Applying correlative light and electron microscopy we revealed the ultrastructure of the acidic mitochondria confirming their proximity to the mitochondrial network, ER and lysosomes. Finally, exploiting siRNA knockdown strategy combined with flux perturbation with lysosomal inhibitors, we demonstrated the importance of both canonical as well as non-canonical autophagy mediators in lysosomal degradation of mitochondria after OXPHOS induction. Taken together, our high-resolution imaging approaches applied on H9c2 cells provide novel insights on mitophagy during physiologically relevant conditions. The implication of redundant underlying mechanisms highlights the fundamental importance of mitophagy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1554-8627 1554-8635 |
| العلاقة: | Godtliebsen, G. (2024). Exploring mitochondrial quality control mechanisms and mitochondria-lipid droplet interactions in cardiac cell models. (Doctoral thesis). https://hdl.handle.net/10037/32271Test; Autophagy; info:eu-repo/grantAgreement/EC/H2020/964800/EU/OrganVision: Technology for real-time visualizing and modelling of fundamental process in living organoids towards new insights into organ-specific health, disease, and recovery/OrganVision/; Godtliebsen, Larsen, Bhujabal, Opstad, Nager Grifo, Punnakkal, Kalstad, Olsen, Lund, Prasad, Agarwal, Myrmel, Birgisdottir. High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts. Autophagy. 2023; FRIDAID 2163420; https://hdl.handle.net/10037/29770Test |
| DOI: | 10.1080/15548627.2023.2230837 |
| الإتاحة: | https://doi.org/10.1080/15548627.2023.2230837Test https://hdl.handle.net/10037/29770Test |
| حقوق: | Attribution 4.0 International (CC BY 4.0) ; openAccess ; Copyright 2023 The Author(s) ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.F2CC977C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15548627 15548635 |
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| DOI: | 10.1080/15548627.2023.2230837 |