The Role of Mitochondrial Dynamics and Mitophagy in Carcinogenesis, Metastasis and Therapy

Abstract

Mitochondria are key cellular organelles and play vital roles in energy metabolism, apoptosis regulation and cellular homeostasis. Mitochondrial dynamics refers to the varying balance between mitochondrial fission and mitochondrial fusion that plays an important part in maintaining mitochondrial homeostasis and quality. Mitochondrial malfunction is involved in aging, metabolic disease, neurodegenerative disorders, and cancers. Mitophagy, a selective autophagy of mitochondria, can efficiently degrade, remove and recycle the malfunctioning or damaged mitochondria, and is crucial for quality control. In past decades, numerous studies have identified a series of factors that regulate mitophagy and are also involved in carcinogenesis, cancer cell migration and death. Therefore, it has become critically important to analyze signal pathways that regulate mitophagy to identify potential therapeutic targets. Here, we review recent progresses in mitochondrial dynamics, the mechanisms of mitophagy regulation, and the implications for understanding carcinogenesis, metastasis, treatment, and drug resistance.

Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome

“…Mitophagy, the specialized autophagy that targets defective mitochondria, is a cardinal feature of mitochondrial quality control since it is responsible for the clearance of damaged mitochondria. Defective mitophagy is usually linked to the impairment of mitochondrial functions [ 85 , 86 ].…”

How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer

“…It has been calculated that autophagy controls the destiny of up to fifty per cent of the cellular proteins ( 24 ), and up to four percent of the mitochondria pool is basally degraded by mitophagy every day, while dysfunctional mitochondria are actively and selectively removed on demand ( 25 ). Thus, overall autophagy presides to protein and organelle quality control that preserves cell viability and prevents from cancer ( 26 , 27 ). Additional tumor suppressive mechanisms of autophagy include the elimination of oncogenic substrates and dampening of oxidative stress and inflammation, which contribute to preserve genome stability ( 28 , 29 ).…”

The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy

“…In early tumorigenesis, mitophagy maintains the metabolic demand of normal cells and suppresses tumorigenesis. In late tumor development, mitophagy enhances cell tolerance and improves tumor progression [ 63 ]. The loss of mitochondrial function by mutation or functional change in a variety of critical genes leads to the accumulation of impaired mitochondria and the inhibition of mitophagy, thus, the induction of tumorigenesis [ 64 ].…”