The Role of Mitochondrial Dysfunction in Mitophagy and Apoptosis and Its Relevance to Cancer

Authored by: Jan Ježek

Handbook of Mitochondrial Dysfunction

Print publication date:  June  2019
Online publication date:  May  2019

Print ISBN: 9781138336087
eBook ISBN: 9780429443336
Adobe ISBN:


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Mitochondria are the energy-producing organelles that also play a vital role in the decision-making process of determining whether a cell will die or live. The ability of mitochondria to undergo balanced fission and fusion is a prerequisite for proper mitochondrial function and the maintenance of cellular homeostasis. In addition, mitochondrial dynamics represents a fundamental signaling platform by which a cell responds to various forms of stress. However, the mechanism by which changes in mitochondrial morphology are coupled to the decrease in mitochondrial membrane potential and the simultaneous increase in reactive oxygen species production is currently unknown. Depending on the nature and severity of insult, the cell can activate either pro-survival or pro-death programs such as mitophagy and intrinsic apoptosis, respectively. Mitophagy is a process wherein small dysfunctional fragments of mitochondria are specifically cleared by lysosomes thereby improving the overall health of the mitochondrial network. Upon extensive stress, on the other hand, mitochondrial fragmentation represents an intermediate step toward the irreversible commitment of the cell to mitochondrial outer membrane permeabilization and apoptosis. This chapter reviews the current knowledge on mitochondrial stress signaling in the context of cancer and discusses the mechanisms underpinning mitochondrial dysfunction as relevant to mitophagy and programmed cell death pathways.

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