Apoptosis and liver diseases: recent concepts of mechanism and significance
1Liver Center and Division of Gastroenterology, University of California, San Francisco 94143-0538, USA.
Abstract:
Apoptosis, or programmed cell death, is a highly conserved mechanism that plays an essential role in numerous normal developmental and regulatory processes and disease states. It is mediated by a variable interaction among several components of the cell, including cell surface death receptors, the caspase cascade, mitochondrial metabolism and energetics, and the cytoskeleton. Even in those instances in which cell surface death receptors play a role, mitochondria are often central to the process, not only in mediating the death program, but in initiating it as well. In regard to mitochondrial involvement, a key role is hypothesized for an interaction among AMP-activated protein kinase, cytoskeletal intermediate filaments, and mitochondrial oxidation of fatty acids. This proposed interaction may be a critical element in the pathogenesis of intramitochondrial oxidative stress, diminished inner membrane potential (delta psi(m)), and other mitochondrial changes that contribute to cell death. Apoptosis may participate in a wide variety of disease processes, ranging from chemical and physical injury to viral infection and cancer, but its mechanistic and functional relationship to these conditions remains incompletely understood. Despite this, an understanding of the mechanisms involved and of the identity of potential pharmacologic targets is increasing, and warrants an optimistic view of their potential for clinical application.
Insights
Programmed cell death (apoptosis) involves complex cellular interactions, with mitochondria playing a central role in initiating and mediating the process. Understanding these mechanisms offers potential for new clinical applications in various diseases.
Area of Science:
- Cell Biology
- Biochemistry
- Pathology
Background:
- Apoptosis, or programmed cell death, is a fundamental biological process crucial for development and homeostasis.
- It involves intricate interactions between cell surface receptors, caspases, mitochondria, and the cytoskeleton.
- Mitochondria are increasingly recognized as central players, not just in executing but also initiating apoptotic pathways.
Purpose of the Study:
- To elucidate the central role of mitochondria in apoptosis.
- To investigate the hypothesized interaction between AMP-activated protein kinase, cytoskeletal intermediate filaments, and mitochondrial fatty acid oxidation.
- To explore the contribution of these interactions to intramitochondrial oxidative stress and cell death.
Main Methods:
- The abstract does not specify experimental methods but discusses hypothesized interactions and mechanisms.
- Focuses on the interplay of key cellular components in apoptosis.
- Integrates concepts from cell signaling, mitochondrial function, and cytoskeletal dynamics.
Main Results:
- Mitochondria are central to apoptosis, involved in both initiation and mediation.
- A hypothesized interaction involving AMP-activated protein kinase, intermediate filaments, and fatty acid oxidation is proposed.
- This interaction may drive intramitochondrial oxidative stress and loss of mitochondrial membrane potential, contributing to cell death.
Conclusions:
- Mitochondrial involvement is critical in apoptosis, potentially initiated by interactions with the cytoskeleton and metabolic pathways.
- Dysregulation of these mitochondrial processes may contribute to various diseases.
- Increased understanding of apoptotic mechanisms and targets offers promise for future clinical interventions.
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