Elucidating quality control mechanisms of mitochondrial protein and organelle under normal and diseased conditions
Mitochondrial quality control encompasses processes such as mitochondria-associated degradation, the mitochondrial unfolded protein response , and mitochondrial communication with other subcellular organelles. These processes repair damaged mitochondrial proteins and remove or degrade irreversibly damaged mitochondria. Therefore, they are critical for maintaining normal mitochondrial function. We are identifying molecular factors that participate in these quality control events and aiming to understand how mitochondrial homeostasis influences neuronal survival and contributes to the pathogenesis of neurological disorders. Specifically, we are exploring how aggregate-prone proteins, such as alpha-synuclein, mutant huntingtin (mtHtt), TDP43, Tau and amyloid-beta, are implicated in these diseases.
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Baron C#, Wang RH#, Cooke S, Ng HP, Ferreira RS, Miranda HC and Qi X*., TDP-43 Impairs Glycolysis by Sequestering Hexokinase 1 in Amyotrophic Lateral Sclerosis. Acta Neuropathologica, 2026 Mar 16;151(1):26. PMID: 41838122. #, co-first author
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Hu D, Sun XY and Qi X*, Disrupting α-Synuclein–ClpP interaction restores mitochondrial function and attenuates neuropathology in Parkinson’s disease models. Molecular Neurodegeneration, 2025 Dec 22;20(1):126. PMID: 41430713
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Choi W#, Fattah M#, Shang YT#, Thompson MP, Carrow K, Hu D, Liu ZR, Avram M, Bailey K, Berger O, Qi X* and Gianneschi NC*, Mutant Huntingtin Mimetic Protein-like Polymer Blocks Mitochondrial damage, Rescues Huntington’s Neurons, and Slows Onset of Neuropathology In Vivo. #, co-first author. *, co-corresponding author. Science Advances, 2024, Nov 1, 10, eado8307. PMID: 39485846
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Shang YT, Sun XY, Chen XQ, Wang QQ, Wang EJ, Miller M, Xu R, Pieper AA and Qi X, A CHCHD6-APP axis connects amyloid and mitochondrial dysfunction in Alzheimer's disease. Acta Neuropathologica, 2022 Nov;144(5):911-938. PMID: 36104602
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Hu D, Sun XY, Zarabi S, Hong YN, Schimmer A, Liao XD, Ford CP, Luo Y, Qi X, Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity. Acta Neuropathologica, 2019 Jun;137(6):939-960. PMID: 30877431
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Guo X, Sun XY, Di H, Wang YJ, Fujioka H, Vyas R, Chakrapani S, Joshi UA, Luo Y, Mochly-Rosen D and Qi X, VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington’s disease. Nature Communications, 2016 Aug 26;7:12646. PMID: 27561680