D'Orsi 2017 Neurochem Int

D'Orsi B, Mateyka J, Prehn JH (2017) Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok. Neurochem Int 109:162-70.

» PMID: 28315370

D'Orsi B, Mateyka J, Prehn JH (2017) Neurochem Int

Abstract: Neuronal cell death is often triggered by events that involve intracellular increases in Ca²⁺. Under resting conditions, the intracellular Ca²⁺ concentration is tightly controlled by a number of extrusion and sequestering mechanisms involving the plasma membrane, mitochondria, and ER. These mechanisms act to prevent a disruption of neuronal ion homeostasis. As these processes require ATP, excessive Ca²⁺ overloading may cause energy depletion, mitochondrial dysfunction, and may eventually lead to Ca²⁺-dependent cell death. Excessive Ca²⁺ entry though glutamate receptors (excitotoxicity) has been implicated in several neurologic and chronic neurodegenerative diseases, including ischemic stroke, epilepsy, and Alzheimer's disease. Recent evidence has revealed that excitotoxic cell death is regulated by the B-cell lymphoma-2 (Bcl-2) family of proteins. Bcl-2 proteins, comprising of both pro-apoptotic and anti-apoptotic members, have been shown to not only mediate the intrinsic apoptosis pathway by controlling mitochondrial outer membrane (mtOM) integrity, but to also control neuronal Ca²⁺ homeostasis and energetics. In this review, the role of Bcl-2 family proteins in the regulation of apoptosis, their expression in the central nervous system and how they control Ca²⁺-dependent neuronal injury are summarized. We review the current knowledge on Bcl-2 family proteins in the regulation of mitochondrial function and bioenergetics, including the fusion and fission machinery, and their role in Ca²⁺ homeostasis regulation at the mitochondria and ER. Specifically, we discuss how the 'pro-apoptotic' Bcl-2 family proteins, Bax and Bok, physiologically expressed in the nervous system, regulate such 'non-apoptotic/daytime' functions.

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