Liu, H.Y.; Gale, J.R.; Reynolds, I.J.; Weiss, J.H.; Aizenman, E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines2021, 9, 489.
Liu, H.Y.; Gale, J.R.; Reynolds, I.J.; Weiss, J.H.; Aizenman, E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines 2021, 9, 489.
Liu, H.Y.; Gale, J.R.; Reynolds, I.J.; Weiss, J.H.; Aizenman, E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines2021, 9, 489.
Liu, H.Y.; Gale, J.R.; Reynolds, I.J.; Weiss, J.H.; Aizenman, E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines 2021, 9, 489.
Abstract
Zinc is a highly abundant cation in the brain, where it is essential for cellular function, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc, can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential, leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.
Keywords
zinc, mitochondria, neurodegeneration, calcium, energy metabolism, mitochondrial dynamics
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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