title: The entangled ER-mitochondrial axis as a potential therapeutic strategy in neurodegeneration: A tangled duo unchained.
abstract: Endoplasmic reticulum (ER) and mitochondrial function have both been shown to be critical events in neurodegenerative diseases. The ER mediates protein folding, maturation, sorting as well acts as calcium storage. The unfolded protein response (UPR) is a stress response of the ER that is activated by the accumulation of misfolded proteins within the ER lumen. Although the molecular mechanisms underlying ER stress-induced apoptosis are not completely understood, increasing evidence suggests that ER and mitochondria cooperate to signal cell death. Similarly, calcium-mediated mitochondrial function and dynamics not only contribute to ATP generation and calcium buffering but are also a linchpin in mediating cell fate. Mitochondria and ER form structural and functional networks (mitochondria-associated ER membranes [MAMs]) essential to maintaining cellular homeostasis and determining cell fate under various pathophysiological conditions. Regulated Ca(2+) transfer from the ER to the mitochondria is important in maintaining control of pro-survival/pro-death pathways. In this review, we summarize the latest therapeutic strategies that target these essential organelles in the context of neurodegenerative diseases.
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, CA, USA.
authors.forename: Amit U
authors.initials: AU
authors.lastname: Joshi
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, CA, USA.
authors.forename: Opher S
authors.initials: OS
authors.lastname: Kornfeld
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, CA, USA. Electronic address: mochly@stanford.edu.
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D055808:Drug Discovery; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology* / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium
keywords: Calcium; ER; Mitochondria; Mitochondrial dynamics; Mitochondrial transport; Neurodegeneration; UPR