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      Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases

      review-article
      Author(s): , , , ,
      Publication date (Electronic):
      Journal: Analytical Cellular Pathology (Amsterdam)
      Publisher: Hindawi

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          Abstract

          In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

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          Mitochondrial fission, fusion, and stress.

          Richard Youle, Alexander M. van der Bliek (2012)
          Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
          Article 0 comments Cited 746 times – based on 0 reviews     Review now
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            Cell death: a review of the major forms of apoptosis, necrosis and autophagy

            Mark D’Arcy (2019)
            Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.
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              Mitochondria as multifaceted regulators of cell death

              Florian J. Bock, Stephen Tait (2019)
              Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit.
              Article 0 comments Cited 713 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Haihong Zhu:
                ORCID: https://orcid.org/0000-0002-5387-8832
                Journal
                Journal ID (nlm-ta): Anal Cell Pathol (Amst)
                Journal ID (iso-abbrev): Anal Cell Pathol (Amst)
                Journal ID (publisher-id): acp
                Title: Analytical Cellular Pathology (Amsterdam)
                Publisher: Hindawi
                ISSN (Print): 2210-7177
                ISSN (Electronic): 2210-7185
                Publication date Collection: 2021
                Publication date (Electronic): 11 November 2021
                Volume: 2021
                Electronic Location Identifier: 8900122
                Affiliations
                State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
                Author notes

                Academic Editor: Yun Ping Lim

                Author information
                https://orcid.org/0000-0002-5387-8832
                Article
                DOI: 10.1155/2021/8900122
                PMC ID: 8601834
                PubMed ID: 34804779
                SO-VID: f9d15b0c-3060-4935-beef-864f77e301e9
                Copyright © Copyright © 2021 Qingfei Chu et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 4 August 2021
                Date revision received : 20 October 2021
                Date accepted : 26 October 2021
                Funding
                Funded by: Science and Technology Major Projects of Ningbo
                Award ID: 2016C51008
                Funded by: Science and Technology Major Projects of Zhejiang Province
                Award ID: 2018C04016
                Funded by: National Science and Technology Major Project of China
                Award ID: 2018ZX10302206
                Categories
                Subject: Review Article

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