Abstract
Mitochondrial dysfunction is a common and prominent feature of prion diseases and other neurodegenerative disorders. Mitochondria are dynamic organelles that constantly fuse with one another and subsequently break apart. Defective or superfluous mitochondria are usually eliminated by a form of autophagy, referred to as mitophagy, to maintain mitochondrial homeostasis. Mitochondrial dynamics are tightly regulated by processes including fusion and fission. Dysfunction of mitochondrial dynamics can lead to the accumulation of abnormal mitochondria and contribute to cellular damage. Neurons are among the cell types that consume the most energy, have a highly complex morphology, and are particularly dependent on mitochondrial functions and dynamics. In this review article, we summarize the molecular mechanisms underlying the mitochondrial dynamics and the regulation of mitophagy and discuss the dysfunction of these processes in the progression of prion diseases and other neurodegenerative disorders. We have also provided an overview of mitochondrial dynamics as a therapeutic target for neurodegenerative diseases.
Highlights
Prion diseases comprise a group of infectious neurodegenerative disorders, including bovine spongiform encephalopathy, scrapie, chronic wasting disease, kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia
All prion diseases are associated with the accumulation and aggregation of misfolded PrPSc in the central nervous system (CNS), which leads to neuroinflammation and neurodegeneration (Prusiner, 2001; White et al, 2003; Shah et al, 2017b)
Dysregulation of the fusion and fission of mitochondria is associated with several neurodegenerative diseases, including prion diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD; Lin and Beal, 2006; Choi et al, 2014)
Summary
Prion diseases comprise a group of infectious neurodegenerative disorders, including bovine spongiform encephalopathy, scrapie, chronic wasting disease, kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. Mitochondrial Dynamics in Prion Diseases are highly dynamic organelles and constantly undergo fission and fusion to regulate their morphology, size and number (Chen and Chan, 2009; Wang et al, 2009a; Toyama et al, 2016). These dynamic processes are critical for modulating mitochondrial distribution, mitophagy and cell death (Detmer and Chan, 2007; Suen et al, 2008; Itoh et al, 2013). Knockdown of FUNDC1 prevents the translocation of Drp to mitochondria and causes mitochondrial elongation, indicating that FUNDC1 regulates mitochondrial dynamics at ER-mitochondrial contact sites under hypoxic conditions (Wu et al, 2016)
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