There are many “right” answers to the essay questions. Ensure your answers are p

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There are many “right” answers to the essay questions. Ensure your answers are plausible and justifiable for full credit.

Long Essay Question Please use essay format and address all mentioned topics. Structure with introduction/background, rationale, experiments, and include predictions for each experiment you suggest. Design a series of experiments (at least 3) to test the hypothesis: dynamin-related GTPase dynamin-related protein 1 (Drp1) mutation causes mitochondrial homeostasis defects. Ensure you describe normal mitochondrial homeostasis, include fission, fusion, and mitophagy. Include experiments to observe cellular mitochondria content, mitochondrial ultrastructure, and any other experiments you think will be helpful and/or yield useful results.

Explanation / Answer

The recent developments of abnormal mitochondrial dynamics, mitochondrial fragmentation, and neuronal damage in neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The GTPase family of proteins, including fission proteins, dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1), and fusion proteins (Mfn1, Mfn2 and Opa1) are essential to maintain mitochondrial fission and fusion balance, and to provide necessary adenosine triphosphate to neurons. Among these, Drp1 is involved in several important aspects of mitochondria, including shape, size, distribution, remodeling, and maintenance of mitochondria in mammalian cells. In addition, recent advancements in molecular, cellular, electron microscopy, and confocal imaging studies revealed that Drp1 is associated with several cellular functions, including mitochondrial and peroxisomal fragmentation, phosphorylation, SUMOylation, ubiquitination, and cell death. In the last two decades, tremendous progress has been made in researching mitochondrial dynamics, in yeast, worms, and mammalian cells; and this research has provided evidence linking Drp1 to neurodegenerative diseases. Researchers in the neurodegenerative disease field are beginning to recognize the possible involvement of Drp1 in causing mitochondrial fragmentation and abnormal mitochondrial dynamics in neurodegenerative diseases. summarizes research findings relating Drp1 to mitochondrial fission and fusion, in yeast, worms, and mammals. Based on findings from the laboratory, we propose that mutant proteins of neurodegenerative diseases, including AD, PD, HD, and ALS, interact with Drp1, activate mitochondrial fission machinery, fragment mitochondria excessively, and impair mitochondrial transport and mitochondrial dynamics, ultimately causing mitochondrial dysfunction and neuronal damage.

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