Journal Article


Jochen H M Prehn
Julia Mateyka
Beatrice D'Orsi



neurodegenerative diseases central nervous system lymphoma b cell this review cell death mitochondrial proteins bcl 2 family receptors glutamate

Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok. (2017)

Abstract Neuronal cell death is often triggered by events that involve intracellular increases in Ca(2+). Under resting conditions, the intracellular Ca(2+) 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 Ca(2+) overloading may cause energy depletion, mitochondrial dysfunction, and may eventually lead to Ca(2+)-dependent cell death. Excessive Ca(2+) 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 (MOM) integrity, but to also control neuronal Ca(2+) 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 Ca(2+)-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 Ca(2+) 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Julia Mateyka, Beatrice D'Orsi

Experts in our system

Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Beatrice D'Orsi
Royal College of Surgeons in Ireland
Total Publications: 14