Abstract
As an essential organelle in nucleated eukaryotic cells, mitochondria play a central role in energy metabolism, maintenance of redox balance, and regulation of apoptosis. Mitochondrial dysfunction, either due to the TCA cycle enzyme defects, mitochondrial DNA genetic mutations, defective mitochondrial electron transport chain, oxidative stress, or aberrant oncogene and tumor suppressor signaling, has been observed in a wide spectrum of human cancers. In this review, we summarize mitochondrial dysfunction induced by these alterations that promote human cancers.
Highlights
Mitochondria are semi-autonomous intracellular double membrane-bound organelles, which include an outer membrane, a highly folded inner membrane, a matrix space surrounded by the inner membrane, and an inter-membrane space between the inner and outer membranes [1].Usually, a cell has hundreds or thousands of mitochondria, which can occupy up to 25% of the cellular cytoplasm
Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutations, malfunctioned tricarboxylic acid (TCA) cycle enzymes, electron respiratory chain leakage and subsequent oxidative stress, and/or aberrant oncogenic and tumor suppressor signaling is known to alter cellular metabolic pathways, disrupt redox balance, and cause resistance to apoptosis and therapies that significantly contribute to the development of multiple types of human cancers
Cancer cells exhibit an altered redox status and metabolism, which are associated with mitochondria as they are the major sites of reactive oxygen species (ROS) generation and energy metabolism
Summary
Mitochondria are semi-autonomous intracellular double membrane-bound organelles, which include an outer membrane, a highly folded inner membrane (crista), a matrix space surrounded by the inner membrane, and an inter-membrane space between the inner and outer membranes [1]. Thirteen proteins are encoded by mtDNA, while approximately 1000 mitochondrial proteins are encoded by the nuclear genome, translated in the cytoplasm and transported into the mitochondria by a specific transport system [7] These two pools of proteins are required to maintain mitochondria as a cellular power hub and a signaling nexus that are essential for normal cell function. Mitochondrial dysfunction caused by mtDNA mutations, malfunctioned TCA cycle enzymes, electron respiratory chain leakage and subsequent oxidative stress, and/or aberrant oncogenic and tumor suppressor signaling is known to alter cellular metabolic pathways, disrupt redox balance, and cause resistance to apoptosis and therapies that significantly contribute to the development of multiple types of human cancers. Sci. 2020, 21, x FOR PEER REVIEW following sections, we will present current knowledge on these aspects of mitochondrial dysfunction pertaining to the pathologies of various forms of human malignancies
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