Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection

Abstract

Mitochondrial dysfunction is a hallmark of many diseases. The retrograde signaling initiated by dysfunctional mitochondria can bring about global changes in gene expression that alters cell morphology and function. Typically, this is attributed to disruption of important mitochondrial functions, such as ATP production, integration of metabolism, calcium homeostasis and regulation of apoptosis. Recent studies showed that in addition to these factors, mitochondrial dynamics might play an important role in stress signaling. Normal mitochondria are highly dynamic organelles whose size, shape and network are controlled by cell physiology. Defective mitochondrial dynamics play important roles in human diseases. Mitochondrial DNA defects and defective mitochondrial function have been reported in many cancers. Recent studies show that increased mitochondrial fission is a pro-tumorigenic phenotype. In this paper, we have explored the current understanding of the role of mitochondrial dynamics in pathologies. We present new data on mitochondrial dynamics and dysfunction to illustrate a causal link between mitochondrial DNA defects, excessive fission, mitochondrial retrograde signaling and cancer progression.

FOXO1, a Potential Therapeutic Target, Regulates Autophagic Flux, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Human Cholangiocarcinoma QBC939 Cells

“…Furthermore, mitochondria are the energy powerhouses of cells and make the most use of the cell’s ATP. Cancer cells consumed a large amount of energy supplied as ATP, so any disruption in this supply is likely to cause apoptosis of cell [39]. Our in vitro data demonstrate that treatment of QBC939 cells with resveratrol inhibited autophagy progression and increased the oxidative stress and MtD (Fig.…”

T-Cell Intracellular Antigens and Hu Antigen R Antagonistically Modulate Mitochondrial Activity and Dynamics by Regulating Optic Atrophy 1 Gene Expression

“…The inner mitochondrial membrane is extensively folded, producing invaginations called cristae, which control oxidative phosphorylation (OXPHOS), electron and metabolite transport, and cell death and survival (3). Consequently, mitochondrial network dysregulation is linked to several pathophysiological conditions, including cancer, diabetes, and neurodegenerative diseases (4)(5)(6)(7)(8).…”

“…Conversely, mitochondrial dynamics is controlled by mitochondrion-shaping proteins that regulate fusion and fission events. Core components of the mitochondrial fusion/ fission machinery include mitofusin 1 (MFN1), mitofusin 2 (MFN2), and optic atrophy 1 (OPA1), which promote fusion, whereas fission is governed by dynamin-related protein 1 (DRP1) and by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins (MiD49 and MiD51), and fission 1 (FIS1) (1)(2)(3)(4)(5)(6)(7)(8).…”

PINK1/Parkin-Mediated Mitophagy Promotes Resistance to Sonodynamic Therapy

“…Mitochondrial fission and fusion allow rapidly morphological changes in response to physiological and pathological conditions [45][46][47]. Dysfunction in mitochondrial dynamics is related to many neurodegenerative diseases, underpinning the role of fission and fusion in the maintenance of cellular homeostasis [46,48,49]. We observed that ALA-SDT could induce a decrease in mitochondrial membrane potential and ATP production, which means the initiation of mitochondrial dysfunction.…”

“…Though cancer cells are relatively independent of mitochondrial oxidative pathways for ATP production, mitochondria still play a crucial role in regulating cellular homeostasis and cell death [43,44]. Mitochondrial fission and fusion allow rapidly morphological changes in response to physiological and pathological conditions [45][46][47]. Dysfunction in mitochondrial dynamics is related to many neurodegenerative diseases, underpinning the role of fission and fusion in the maintenance of cellular homeostasis [46,48,49].…”