Inter-organelle Communication in the Pathogenesis of Mitochondrial Dysfunction and Insulin Resistance

Keenan, Stacey N; Watt, Matthew James; Montgomery, Magdalene K

doi:10.1007/s11892-020-01300-4

Cited by 23 publications

(16 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TNT-mediated mitochondrial transfer is based on an exquisite mechanism of intracellular organelle segregation within the same tumor cell and subsequent transfer of altered mitochondria into healthy cells. Inter-organelle interactions play a key role in health and disease conditions, including synaptic function, intracellular trafficking, lipid metabolism, and signaling 64 , 65 ; however, the movement of these complexes within the cell or through TNT is unknown. We describe here that TNT-mediated transfer of mitochondria is a key event in non-tumor adaptation to tumor cells; however, our EM images indicate that mitochondria interact with the ER, Golgi, and lipid bodies.…”

Section: Discussionmentioning

confidence: 99%

Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions

Valdebenito

Malik

Luu

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Cell-to-cell communication is essential for the development and proper function of multicellular systems. We and others demonstrated that tunneling nanotubes (TNT) proliferate in several pathological conditions such as HIV, cancer, and neurodegenerative diseases. However, the nature, function, and contribution of TNT to cancer pathogenesis are poorly understood. Our analyses demonstrate that TNT structures are induced between glioblastoma (GBM) cells and surrounding non-tumor astrocytes to transfer tumor-derived mitochondria. The mitochondrial transfer mediated by TNT resulted in the adaptation of non-tumor astrocytes to tumor-like metabolism and hypoxia conditions. In conclusion, TNT are an efficient cell-to-cell communication system used by cancer cells to adapt the microenvironment to the invasive nature of the tumor.

show abstract

Section: Discussionmentioning

confidence: 99%

Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions

Valdebenito

Malik

Luu

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Another PTP1B substrate is PTPIP51 (mentioned above), where the extent of their interaction is strongly reduced in an animal model of obesity (Bobrich et al 2011). Whether MERC abundance influences insulin sensitivity or how insulin resistance affects these contacts is unclear (Keenan et al 2020). However, disruption of ER-mitochondria communication seems to be an early event in the development of insulin resistance, preceding mitochondrial dysfunction and defective insulin signaling (Tubbs et al 2018).…”

Section: Contact Sites In the Endolysosomal Systemmentioning

confidence: 99%

Interorganelle communication, aging, and neurodegeneration

Petković

Jan

2021

Genes Dev.

View full text Add to dashboard Cite

Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. This review aims to present novel findings on the cellular interorganelle communication network and how its dysfunction may contribute to aging and neurodegeneration. The consequences of disturbed interorganellar communication are intimately linked with age-related pathologies. Given that both aging and neurodegenerative diseases are characterized by the concomitant failure of multiple cellular pathways, coordination of organelle communication and function could represent an emerging regulatory mechanism critical for long-term cellular homeostasis. We anticipate that defining the relationships between interorganelle communication, aging, and neurodegeneration will open new avenues for therapeutics.

show abstract

“…Mitochondrion regulates many physiological functions such as adenosine triphosphate (ATP) synthesis, free radicals generation, fatty acid β−oxidation, calcium homeostasis, and cell survival and death ( Liu L. et al, 2020 ; Kirtonia et al, 2021 ). Mitochondria are dynamic organelles that can fleetly adapt to changes in cellular energy metabolism by regulating mitochondrial biogenesis, mitochondrial fission, mitochondrial fusion and removal of damaged mitochondria ( Vásquez-Trincado et al, 2016 ; Mills et al, 2017 ; Keenan et al, 2020 ). Of note, the uppermost physiological function of mitochondria is to produce ATP via oxidative phosphorylation (OXPHOS) ( Bhatti et al, 2017 ).…”

Section: Mitochondrial Dysfunction and Oxidative Stressmentioning

confidence: 99%

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Guo

Huang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Metabolic disorders include metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. Due to unhealthy lifestyles such as high-calorie diet, sedentary and physical inactivity, the prevalence of metabolic disorders poses a huge challenge to global human health, which is the leading cause of global human death. Mitochondrion is the major site of adenosine triphosphate synthesis, fatty acid β−oxidation and ROS production. Accumulating evidence suggests that mitochondrial dysfunction-related oxidative stress and inflammation is involved in the development of metabolic disorders. Mitophagy, a catabolic process, selectively degrades damaged or superfluous mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial function. It is considered to be one of the major mechanisms responsible for mitochondrial quality control. Growing evidence shows that mitophagy can prevent and treat metabolic disorders through suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. In the past decade, in order to expand the range of pharmaceutical options, more and more phytochemicals have been proven to have therapeutic effects on metabolic disorders. Many of these phytochemicals have been proved to activate mitophagy to ameliorate metabolic disorders. Given the ongoing epidemic of metabolic disorders, it is of great significance to explore the contribution and underlying mechanisms of mitophagy in metabolic disorders, and to understand the effects and molecular mechanisms of phytochemicals on the treatment of metabolic disorders. Here, we investigate the mechanism of mitochondrial dysfunction in metabolic disorders and discuss the potential of targeting mitophagy with phytochemicals for the treatment of metabolic disorders, with a view to providing a direction for finding phytochemicals that target mitophagy to prevent or treat metabolic disorders.

show abstract

Inter-organelle Communication in the Pathogenesis of Mitochondrial Dysfunction and Insulin Resistance

Cited by 23 publications

References 91 publications

Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions

Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions

Interorganelle communication, aging, and neurodegeneration

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Contact Info

Product

Resources

About