Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway.

in British journal of pharmacology by M J Roy, A Vom, P E Czabotar, G Lessene

TLDR

  • Mitochondria are like the powerhouse of cells, they make energy for the cell to work. But they also have another important job, they can help the cell die when it needs to. The BCL-2 family of proteins control this process, and if we can find a way to control them, we might be able to help people with certain diseases. The study found that controlling these proteins with small molecules or peptides could help people with cancer, autoimmunity, and neurodegenerative conditions. However, there are still things we need to learn about this process before we can use it to help people.

Abstract

The principal biological role of mitochondria is to supply energy to cells; although intriguingly, evolution has bestowed another essential function upon these cellular organelles: under physiological stress, mitochondria become the cornerstone of apoptotic cell death. Specifically, mitochondrial outer membrane permeabilization (MOMP) allows cell death factors such as cytochrome c to be released into the cytoplasm, thus inducing caspase activation and the eventual destruction of essential cellular components. Proteins of the B-cell lymphoma 2 (BCL-2) family control the tightly regulated pathway that causes MOMP. The equilibrium between pro-survival and pro-apoptotic members of the BCL-2 family dictates the fate of cells, the homeostasis of organs and, by extension, the health of whole organisms. Dysregulation of this equilibrium is involved in a large number of diseases such as cancer, autoimmunity and neurodegenerative conditions. Modulating the activity of the BCL-2 family of proteins with small molecules or peptides is an attractive but challenging therapeutic goal. This review highlights the latest developments in this field and provides evidence that this strategy is likely to have a positive effect on the treatment of still poorly addressed medical conditions.

Overview

  • The study focuses on the role of mitochondria in apoptotic cell death and the regulation of this process by the BCL-2 family of proteins. The hypothesis being tested is that modulating the activity of these proteins with small molecules or peptides can have a positive impact on the treatment of various medical conditions. The methodology used for the experiment includes a review of the latest literature on the topic, and the study aims to provide evidence for the therapeutic potential of this approach.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions related to the regulation of mitochondrial outer membrane permeabilization (MOMP) and the activity of the BCL-2 family of proteins. The results show that modulating the activity of these proteins with small molecules or peptides can have a positive impact on the treatment of various medical conditions, including cancer, autoimmunity, and neurodegenerative conditions. The key findings of the study support the hypothesis that this approach has therapeutic potential.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice, as they suggest that modulating the activity of the BCL-2 family of proteins with small molecules or peptides could be an effective therapeutic strategy for a variety of medical conditions. However, the study also identifies limitations that need to be addressed in future research, such as the need for more preclinical studies and the development of more specific and selective compounds. Possible future research directions include the exploration of the mechanisms underlying the regulation of MOMP and the development of novel compounds that target specific members of the BCL-2 family.
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