The Concerted Action of Mitochondrial Dynamics and Positioning: New Characters in Cancer Onset and Progression

Pendin, Diana; Filadi, Riccardo; Pizzo, Paola

doi:10.3389/fonc.2017.00102

Cited by 31 publications

(23 citation statements)

References 89 publications

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“…Mitochondrial fragmentation is usually associated with an imbalance of the Drp1/MFNs ratio (reviewed in ref. 4 ). For instance, decreased MFN2 levels have been reported in liver 124 , colorectal 125 , and lung 126 cancers.…”

Section: Cancermentioning

confidence: 99%

“…Alternatively, the increased OMM curvature, observed upon MFN1-depletion, has been suggested to impair Bax insertion into the OMM, preventing Bax-induced apoptosis 130 . A more detailed discussion on these topics can be found in a recent review 4 .…”

Section: Cancermentioning

confidence: 99%

“…On the contrary, mitochondrial fragmentation has been associated to a reduced respiration, frequently observed in cancerous cells in which the so called “Warburg effect” takes place (recently reviewed in ref. 4 ). Another aspect influenced by fission/fusion balance, particularly important for neuronal cells, is mitochondria transport and distribution along axons.…”

Section: Introductionmentioning

confidence: 99%

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Mitofusin 2: from functions to disease

2018

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Mitochondria are highly dynamic organelles whose functions are essential for cell viability. Within the cell, the mitochondrial network is continuously remodeled through the balance between fusion and fission events. Moreover, it dynamically contacts other organelles, particularly the endoplasmic reticulum, with which it enterprises an important functional relationship able to modulate several cellular pathways. Being mitochondria key bioenergetics organelles, they have to be transported to all the specific high-energy demanding sites within the cell and, when damaged, they have to be efficiently removed. Among other proteins, Mitofusin 2 represents a key player in all these mitochondrial activities (fusion, trafficking, turnover, contacts with other organelles), the balance of which results in the appropriate mitochondrial shape, function, and distribution within the cell. Here we review the structural and functional properties of Mitofusin 2, highlighting its crucial role in several cell pathways, as well as in the pathogenesis of neurodegenerative diseases, metabolic disorders, cardiomyopathies, and cancer.

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Section: Cancermentioning

confidence: 99%

Section: Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitofusin 2: from functions to disease

2018

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“…Intermediates of the TCA cycle contribute to signaling tumorigenesis ( 12 ) and mtROS, which are key mediators in mitochondrial communication ( 13 ), activate signaling pathways that promote cell proliferation and tumorigenesis ( 14 , 15 ). Moreover, mitochondrial dynamics is also reprogrammed in cancer ( 16 ).…”

Section: Overview Of Metabolic Reprogramming In Cancermentioning

confidence: 99%

The Role of Mitochondrial H+-ATP Synthase in Cancer

Esparza-Moltó

Cuezva

2018

Front. Oncol.

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Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+-ATP synthase—the core hub of oxidative phosphorylation—is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+-ATP synthase. IF1 overexpression, both in cells in culture and in tissue-specific mouse models, is sufficient to reprogram energy metabolism to an enhanced glycolysis by limiting ATP production by the H+-ATP synthase. Furthermore, the IF1-mediated inhibition of the H+-ATP synthase promotes the production of mitochondrial ROS (mtROS). mtROS modulate signaling pathways favoring cellular proliferation and invasion, the activation of antioxidant defenses, resistance to cell death, and modulation of the tissue immune response, favoring the acquisition of several cancer traits. Consistently, IF1 expression is an independent marker of cancer prognosis. By contrast, inhibition of the H+-ATP synthase by α-ketoglutarate and the oncometabolite 2-hydroxyglutarate, reduces mTOR signaling, suppresses cancer cell growth, and contributes to lifespan extension in several model organisms. Hence, the H+-ATP synthase appears as a conserved hub in mitochondria-to-nucleus signaling controlling cell fate. Unraveling the molecular mechanisms responsible for IF1 upregulation in cancer and the signaling cascades that are modulated by the H+-ATP synthase are of utmost interest to decipher the metabolic and redox circuits contributing to cancer origin and progression.

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“…In this scenario, these molecular motors hijack mitochondria and transfer them into cancer cell peripheries as a localized energy supply for increased mobility and metastasis of the tumor. Accordingly, mitochondrial fragmentation is believed to facilitate repositioning of mitochondria in cancer cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

2018

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Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate redox signaling or, in excess, cause cell injury and even cell death. Recent evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS generation depending on the physiological status of the cell. Yet, the mechanism by which changes in mitochondrial shape modulate mitochondrial function and redox homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced ROS formation, which, in turn, may deteriorate mitochondrial health and further exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review the latest findings on the intricate relationship between mitochondrial dynamics and ROS production, focusing mainly on its role in malignant disease.

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The Concerted Action of Mitochondrial Dynamics and Positioning: New Characters in Cancer Onset and Progression

Cited by 31 publications

References 89 publications

Mitofusin 2: from functions to disease

Mitofusin 2: from functions to disease

The Role of Mitochondrial H+-ATP Synthase in Cancer

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

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