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Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
Published on: August 12, 2018
The mitochondrial death pathway: a promising therapeutic target in diseases
Sanjeev Gupta1, George E N Kass, Eva Szegezdi
1NCBES, National University of Ireland, Galway, Ireland. Sanjeev.gupta@nuigalway.ie <Sanjeev.gupta@nuigalway.ie>
Abstract:
The mitochondrial pathway to apoptosis is a major pathway of physiological cell death in vertebrates. The mitochondrial cell death pathway commences when apoptogenic molecules present between the outer and inner mitochondrial membranes are released into the cytosol by mitochondrial outer membrane permeabilization (MOMP). BCL-2 family members are the sentinels of MOMP in the mitochondrial apoptotic pathway; the pro-apoptotic B cell lymphoma (BCL)-2 proteins, BCL-2 associated x protein and BCL-2 antagonist killer 1 induce MOMP whereas the anti-apoptotic BCL-2 proteins, BCL-2, BCL-x(l) and myeloid cell leukaemia 1 prevent MOMP from occurring. The release of pro-apoptotic factors such as cytochrome c from mitochondria leads to formation of a multimeric complex known as the apoptosome and initiates caspase activation cascades. These pathways are important for normal cellular homeostasis and play key roles in the pathogenesis of many diseases. In this review, we will provide a brief overview of the mitochondrial death pathway and focus on a selection of diseases whose pathogenesis involves the mitochondrial death pathway and we will examine the various pharmacological approaches that target this pathway.
Insights
The mitochondrial pathway of cell death involves the release of molecules from mitochondria, regulated by BCL-2 proteins. This pathway is crucial for cell homeostasis and disease, with targeted therapies under investigation.
Area of Science:
- Cell Biology
- Biochemistry
- Pathology
Background:
- The mitochondrial pathway is a primary mechanism for physiological cell death in vertebrates.
- This process is initiated by mitochondrial outer membrane permeabilization (MOMP), releasing apoptogenic molecules into the cytosol.
- BCL-2 family proteins critically regulate MOMP, with some promoting and others inhibiting the process.
Purpose of the Study:
- To provide an overview of the mitochondrial death pathway.
- To highlight diseases linked to the mitochondrial death pathway.
- To examine pharmacological strategies targeting this pathway.
Main Methods:
- Review of scientific literature on the mitochondrial apoptosis pathway.
- Analysis of the role of BCL-2 family proteins in MOMP.
- Discussion of disease pathogenesis involving mitochondrial cell death.
- Exploration of therapeutic interventions targeting the mitochondrial pathway.
Main Results:
- MOMP triggers the release of factors like cytochrome c, leading to apoptosome formation and caspase activation.
- Dysregulation of the mitochondrial pathway is implicated in various diseases.
- Targeting the mitochondrial pathway offers potential therapeutic avenues.
Conclusions:
- The mitochondrial pathway is fundamental to cellular homeostasis and disease.
- Understanding BCL-2 protein regulation of MOMP is key.
- Pharmacological targeting of the mitochondrial pathway holds promise for treating diseases.
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