Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites

Bosc, Claudie; Broin, Nicolas; Fanjul, Marjorie; Saland, Estelle; Farge, Thomas; Courdy, Charly; Batut, Aurélie; Masoud, Rawand; Larrue, Clément; Skuli, Nicolas; Espagnolle, Nicolas; Pagès, Jean‐Christophe; Carrier, Alice; Bost, Fréd́eric; Bertrand‐Michel, Justine; Tamburini, Jérôme; Récher, Christian; Bertoli, Sarah; Mas, Véronique Mansat‐De; Manenti, Stéphane; Sarry, Jean-Emmanuel; Joffre, Carine

doi:10.1038/s41467-020-17882-2

Cited by 114 publications

(89 citation statements)

References 58 publications

(68 reference statements)

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“…Lipophagy was first shown to be an active way to get energy under starvation [102] through the association of autophagic components with lipid droplets (LDs). Recently, lipophagy has been demonstrated to regulate the fatty acid availability for the β-oxidation through contact sites between the mitochondria and the ER [103]. Regarding virus-associated hijacking of the cell lipid metabolism, Heaton and Randall [100] early showed that increased β-oxidation and the depletion of triglycerides was concurrent with and necessary for DENV replication.…”

Section: Lipid-related Host Factors Associated To the Rcs' Buildupmentioning

confidence: 99%

Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update

Balgoma

Montero

2020

Metabolites

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The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection.

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Section: Lipid-related Host Factors Associated To the Rcs' Buildupmentioning

confidence: 99%

Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update

Balgoma

Montero

2020

Metabolites

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“…Considering that TRMT61B downregulation diminishes the expression of various protein components of at least complex I and IV, an indirect link between TRMT61B and autophagy can be proposed. Nevertheless, we cannot exclude the possibility that autophagy was a direct TRMT61B target whose inhibition could have a negative impact on mitochondrial metabolism, as it has been recently reported in acute myeloid leukemia 92 . Consequently, a complex network of interactions might be simultaneously working in a TRMT61B dependent manner and being influenced each other.…”

Section: Discussionmentioning

confidence: 87%

Targeting the mitochondrial RNA methyltransferase TRMT61B reveals new therapeutic opportunities in aneuploid cancer cells

Martín

Vilaplana-Martí

et al. 2021

Preprint

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Chromosomal instability (CIN) is an important source of genetic and phenotypic variation that has been extensively reported as a critical cancer related property that improves tumor cell adaptation and survival. CIN and its immediate consequence, aneuploidy, provoke adverse effects on cellular homeostasis that need to be overcome by developing efficient anti-stress mechanisms. Perturbations in these safeguard responses might be detrimental for cancer cells and represent an important tumor specific Achilles heel since CIN and aneuploidy are very rare events in normal cells. On the other hand, epitranscriptomic marks catalyzed by different RNA modifying enzymes have been found to change under several stress insults. Although CIN and aneuploidy are important intracellular stressors, their biological connection with RNA modifications is pending to be determined. In an in silico search for new cancer biomarkers, we have identified TRMT61B, a mitochondrial RNA methyltransferase enzyme, to be associated with high levels of aneuploidy. In the present work, we study the connection of this molecule with cancer and aneuploidy. First, we show increased protein amounts of TRMT61B in tumor cell lines with imbalanced karyotype as well as in different tumor types compared to unaffected control tissues. In addition, we demonstrate that depletion of TRMT61B in melanoma cells reduces cell proliferation either by fostering apoptosis and inhibiting autophagy in high-aneuploid (ANEhigh) cells or by inducing senescence in the case of low-aneuploid (ANElow) cell lines. Further, TRMT61B elimination compromises mitochondrial function and reduces the expression of several mitochondrial encoded proteins that are part of the electron transport chain. Finally, transwell and xenograft experiments revealed a reduced invasive and tumorigenic capacity upon TRMT61B depletion that strengthen the therapeutic value of this aneuploidy-associated biomarker. These results, which connect tumorigenesis, aneuploidy and mitochondrial RNA methylation, bring to the cancer field a new putative strategy to specifically target high aneuploid tumors.

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“…Autophagy is also activated after glutamate depletion and protects cancer cells from impairment of energy production through upregulation of lipid catabolism [ 139 ]. In addition, blockage of autophagic flux decreases OXPHOS, leading to lipid accumulation and cell growth arrest in acute myeloid leukemia, revealing an unquestionable linkage between autophagy and FAO levels in cancer cells [ 140 ]. It is notable that autophagy activation is also accompanied by increased intracellular lipid reservation in certain contexts.…”

Section: Autophagic Regulation: a Potential Mechanism For Cancer Cmentioning

confidence: 99%

Tumor Metabolic Reprogramming by Adipokines as a Critical Driver of Obesity-Associated Cancer Progression

Pham

Park

2021

IJMS

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Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and tumor-suppressing properties in an adipokine type- and context-dependent manner. Increasing evidence has indicated that these adipose tissue-derived hormones differentially modulate cancer cell-specific metabolism. Some adipokines, such as leptin, resistin, and visfatin, which are overproduced in obesity and widely implicated in different stages of cancer, promote cellular glucose and lipid metabolism. Conversely, adiponectin, an adipokine possessing potent anti-tumor activities, is linked to a more favorable metabolic phenotype. Adipokines may also play a pivotal role under the reciprocal regulation of metabolic rewiring of cancer cells in tumor microenvironment. Given the fact that metabolic reprogramming is one of the major hallmarks of cancer, understanding the modulatory effects of adipokines on alterations in cancer cell metabolism would provide insight into the crosstalk between obesity, adipokines, and tumorigenesis. In this review, we summarize recent insights into putative roles of adipokines as mediators of cellular metabolic rewiring in obesity-associated tumors, which plays a crucial role in determining the fate of tumor cells.

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Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites

Cited by 114 publications

References 58 publications

Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update

Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update

Targeting the mitochondrial RNA methyltransferase TRMT61B reveals new therapeutic opportunities in aneuploid cancer cells

Tumor Metabolic Reprogramming by Adipokines as a Critical Driver of Obesity-Associated Cancer Progression

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