Bcl-2 Orthologues, Buffy and Debcl, Can Suppress Drp1-Dependent Age-Related Phenotypes in Drosophila
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bioinformatic Analysis
2.2. Drosophila Stocks and Media
2.3. Aging Assay
2.4. Climbing Assay
3. Results
3.1. Drp1 Is Highly Conserved between Homo sapiens and Drosophila melanogaster
3.2. The Directed Overexpression and Knockdown of Drp1 with Ddc-Gal44.3D
3.3. Phenotypic Rescue by Co-Expression of Drp1 and Drp1-RNAi Directed by Ddc-Gal44.3D
3.4. Alteration of the Expression of Buffy and Debcl in Combination with Drp1 Directed by the Ddc-Gal44.3D Transgene
3.5. Altering the Expression of Buffy and Debcl along with Drp1-RNAi by Ddc-Gal44.3D Transgene
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Galluzzi, L.; Kepp, O.; Kroemer, G. Mitochondria: Master regulators of danger signalling. Nat. Rev. Mol. Cell Biol. 2012, 13, 780–788. [Google Scholar] [CrossRef]
- Adhikary, A.; Mukherjee, A.; Banerjee, R.R.; Nagotu, S. DRP1: At the crossroads of dysregulated mitochondrial dynamics and altered cell signaling in cancer cells. ACS Omega 2023, 8, 45208–45223. [Google Scholar] [CrossRef] [PubMed]
- Zerihun, M.; Sukumaran, S.; Qvit, N. The Drp1-mediated mitochondrial fission protein interactome as an emerging core player in mitochondrial dynamics and cardiovascular disease therapy. Int. J. Mol. Sci. 2023, 24, 5785. [Google Scholar] [CrossRef]
- Ikeda, Y.; Shirakabe, A.; Maejima, Y.; Zhai, P.; Sciarretta, S.; Toli, J.; Nomura, M.; Mihara, K.; Egashira, K.; Ohishi, M.; et al. Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ. Res. 2015, 116, 264–278. [Google Scholar] [CrossRef]
- Schmitt, K.; Grimm, A.; Dallmann, R.; Oettinghaus, B.; Restelli, L.M.; Witzig, M.; Ishihara, N.; Mihara, K.; Ripperger, J.A.; Albrecht, U.; et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. 2018, 27, 657–666.e5. [Google Scholar] [CrossRef] [PubMed]
- Oettinghaus, B.; D’Alonzo, D.; Barbieri, E.; Restelli, L.M.; Savoia, C.; Licci, M.; Tolnay, M.; Frank, S.; Scorrano, L. DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress. Biochim. Biophys. Acta 2016, 1857, 1267–1276. [Google Scholar] [CrossRef] [PubMed]
- Hoitzing, H.; Johnston, I.G.; Jones, N.S. What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research. BioEssays 2015, 37, 687–700. [Google Scholar] [CrossRef] [PubMed]
- Maes, M.E.; Grosser, J.A.; Fehrman, R.L.; Schlamp, C.L.; Nickells, R.W. Completion of BAX recruitment correlates with mitochondrial fission during apoptosis. Sci. Rep. 2019, 9, 16565. [Google Scholar] [CrossRef]
- Scott, I.; Youle, R.J. Mitochondrial fission and fusion. Essays Biochem. 2010, 47, 85–98. [Google Scholar] [CrossRef]
- Chan, D.C. Fusion and fission: Interlinked processes critical for mitochondrial health. Annu. Rev. Genet. 2012, 46, 265–287. [Google Scholar] [CrossRef]
- Sebastián, D.; Palacín, M.; Zorzano, A. Mitochondrial dynamics: Coupling mitochondrial fitness with healthy aging. Trends Mol. Med. 2017, 23, 201–215. [Google Scholar] [CrossRef]
- Quinn, L.; Coombe, M.; Mills, K.; Daish, T.; Colussi, P.; Kumar, S.; Richardson, H. Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions. EMBO J. 2003, 22, 3568–3579. [Google Scholar] [CrossRef]
- Clavier, A.; Ruby, V.; Rincheval-Arnold, A.; Mignotte, B.; Guénal, I. The Drosophila retinoblastoma protein, Rbf1, induces a Debcl- and Drp1-dependent mitochondrial apoptosis. J. Cell Sci. 2015, 128, 3239–3249. [Google Scholar] [CrossRef] [PubMed]
- Pradeep, H.; Sharma, B.; Rajanikant, G.K. Drp1 in ischemic neuronal death: An unusual suspect. Curr. Med. Chem. 2014, 21, 2183–2189. [Google Scholar] [CrossRef] [PubMed]
- Choi, S.Y.; Lee, J.-H.; Chung, A.-Y.; Jo, Y.; Shin, J.-H.; Park, H.-C.; Kim, H.; Lopez-Gonzalez, J.R.; Ryu, R.; Sun, W. Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis. Cell Death Dis. 2020, 11, 888. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Huang, W.; Shao, Q.; Yang, Y.; Xu, Z.; Chen, J.; Zhang, X.; Xiaoqun, G. Drp1, a potential therapeutic target for Parkinson’s disease, is involved in olfactory bulb pathological alteration in the Rotenone-induced rat model. Toxicol. Lett. 2020, 325, 1–13. [Google Scholar] [CrossRef]
- Xiong, Y.; Yu, J. Modeling Parkinson’s disease in Drosophila: What have we learned for dominant traits? Front. Neurol. 2018, 9, 228. [Google Scholar] [CrossRef]
- Li, H.; Chaney, S.; Forte, M.; Hirsh, J. Ectopic g-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster. Curr. Biol. 2000, 10, 211–214. [Google Scholar] [CrossRef]
- Brand, A.H.; Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993, 118, 401–415. [Google Scholar] [CrossRef]
- Hwang, R.-D.; Wiemerslage, L.; LaBreck, C.J.; Khan, M.; Kannan, K.; Wang, X.; Zhu, X.; Lee, D.; Fridell, Y.-W.C. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson’s disease. Neurobiol. Dis. 2014, 69, 180–191. [Google Scholar] [CrossRef]
- Wang, Z.-H.; Clark, C.; Geisbrecht, E.R. Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation. Hum. Mol. Genet. 2016, 25, 1946–1964. [Google Scholar] [CrossRef]
- Zhou, J.; Xu, L.; Duan, X.; Liu, W.; Zhao, X.; Wang, X.; Shang, W.; Fang, X.; Yang, H.; Jia, L.; et al. Large-scale RNAi screen identified Dhpr as a regulator of mitochondrial morphology and tissue homeostasis. Sci. Adv. 2019, 5, eaax0365. [Google Scholar] [CrossRef] [PubMed]
- M’Angale, P.G.; Staveley, B.E. The Bcl-2 homologue Buffy rescues α-synuclein-induced Parkinson disease-like phenotypes in Drosophila. BMC Neurosci. 2016, 17, 24. [Google Scholar] [CrossRef] [PubMed]
- Terhzaz, S.; Finlayson, A.J.; Stirrat, L.; Yang, J.; Tricoire, H.; Woods, D.J.; Dow, J.A.T.; Davies, S.-A. Cell-specific inositol 1,4,5 trisphosphate 3-kinase mediates epithelial cell apoptosis in response to oxidative stress in Drosophila. Cell Signal. 2010, 22, 737–748. [Google Scholar] [CrossRef]
- Shan, Z.; Li, S.; Gao, Y.; Jian, C.; Ti, X.; Zuo, H.; Wang, Y.; Zhao, G.; Wang, Y.; Zhang, Q. mtDNA extramitochondrial replication mediates mitochondrial defect effects. iScience 2024, 27, 108970. [Google Scholar] [CrossRef]
- Todd, A.; Staveley, B. Expression of Pink1 with α-synuclein in the dopaminergic neurons of Drosophila leads to increases in both lifespan and healthspan. Genet. Mol. Res. 2012, 11, 1497–1502. [Google Scholar] [CrossRef]
- Wai, T.; Langer, T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol. Metab. 2016, 27, 105–117. [Google Scholar] [CrossRef]
- Touvier, T.; De Palma, C.; Rigamonti, E.; Scagliola, A.; Incerti, E.; Mazelin, L.; Thomas, J.-L.; D’Antonio, M.; Politi, L.; Schaeffer, L.; et al. Muscle-specific Drp1 overexpression impairs skeletal muscle growth via translational attenuation. Cell Death Dis. 2015, 6, e1663. [Google Scholar] [CrossRef] [PubMed]
- Yu, T.; Robotham, J.L.; Yoon, Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc. Natl. Acad. Sci. USA 2006, 103, 2653–2658. [Google Scholar] [CrossRef]
- Sun, Y.; Ge, X.; Li, X.; He, J.; Wei, X.; Du, J.; Sun, J.; Li, X.; Xun, Z.; Liu, W.; et al. High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction. Cell Death Dis. 2020, 11, 914. [Google Scholar] [CrossRef]
- Cribbs, J.T.; Strack, S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 2007, 8, 939–944. [Google Scholar] [CrossRef] [PubMed]
- Virdee, K.; Parone, P.A.; Tolkovsky, A.M. Phosphorylation of the pro-apoptotic protein BAD on serine 155, a novel site, contributes to cell survival. Curr. Biol. 2000, 10, 1151–1154. [Google Scholar] [CrossRef] [PubMed]
- Cereghetti, G.M.; Stangherlin, A.; Martins De Brito, O.; Chang, C.R.; Blackstone, C.; Bernardi, P.; Scorrano, L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl. Acad. Sci. USA 2008, 105, 15803–15808. [Google Scholar] [CrossRef] [PubMed]
- Rolland, S.G.; Conradt, B. New role of the BCL2 family of proteins in the regulation of mitochondrial dynamics. Curr. Opin. Cell Biol. 2010, 22, 852–858. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hasan, A.; Staveley, B.E. Bcl-2 Orthologues, Buffy and Debcl, Can Suppress Drp1-Dependent Age-Related Phenotypes in Drosophila. Biomolecules 2024, 14, 1089. https://doi.org/10.3390/biom14091089
Hasan A, Staveley BE. Bcl-2 Orthologues, Buffy and Debcl, Can Suppress Drp1-Dependent Age-Related Phenotypes in Drosophila. Biomolecules. 2024; 14(9):1089. https://doi.org/10.3390/biom14091089
Chicago/Turabian StyleHasan, Azra, and Brian E. Staveley. 2024. "Bcl-2 Orthologues, Buffy and Debcl, Can Suppress Drp1-Dependent Age-Related Phenotypes in Drosophila" Biomolecules 14, no. 9: 1089. https://doi.org/10.3390/biom14091089