Lipid-mediated signals that regulate mitochondrial biology

Nielson, Jason R.; Rutter, Jared

doi:10.1074/jbc.r117.001655

Cited by 34 publications

(26 citation statements)

References 49 publications

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“…Various lipid-mediated signaling mechanisms are involved in the regulation of mitochondrial function. Examples include (254,287): (i) mitophagy, where CL translocates from the MIM to the MOM to bind LC3 and LC3-B-II in collaboration with CER to induce autophagosomal mitochondrial recruitment; (ii) ETC assembly, where the chaperone PHB2 involved in CIV assembly interacts with sphingosine-1phosphate (S1P); and (iii) apoptosis, where CER accumulates and acts together with Bax to induce pore formation, allowing cytochrome-c exit and apoptosis activation.…”

Section: B Role Of Mitochondrial Lipids In Mitochondrial (Ultra)strumentioning

confidence: 99%

Mitochondrial Morphofunction in Mammalian Cells

Bulthuis

Adjobo‐Hermans

Willems

et al. 2019

Antioxidants & Redox Signaling

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Significance: In addition to their classical role in cellular ATP production, mitochondria are of key relevance in various (patho)physiological mechanisms including second messenger signaling, neuro-transduction, immune responses and death induction. Recent Advances: Within cells, mitochondria are motile and display temporal changes in internal and external structure (''mitochondrial dynamics''). During the last decade, substantial empirical and in silico evidence was presented demonstrating that mitochondrial dynamics impacts on mitochondrial function and vice versa. Critical Issues: However, a comprehensive and quantitative understanding of the bidirectional links between mitochondrial external shape, internal structure and function (''morphofunction'') is still lacking. The latter particularly hampers our understanding of the functional properties and behavior of individual mitochondrial within single living cells. Future Directions: In this review we discuss the concept of mitochondrial morphofunction in mammalian cells, primarily using experimental evidence obtained within the last decade. The topic is introduced by briefly presenting the central role of mitochondria in cell physiology and the importance of the mitochondrial electron transport chain (ETC) therein. Next, we summarize in detail how mitochondrial (ultra)structure is controlled and discuss empirical evidence regarding the equivalence of mitochondrial (ultra)structure and function. Finally, we provide a brief summary of how mitochondrial morphofunction can be quantified at the level of single cells and mitochondria, how mitochondrial ultrastructure/volume impacts on mitochondrial bioreactions and intramitochondrial protein diffusion, and how mitochondrial morphofunction can be targeted by small molecules.

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Section: B Role Of Mitochondrial Lipids In Mitochondrial (Ultra)strumentioning

confidence: 99%

Mitochondrial Morphofunction in Mammalian Cells

Bulthuis

Adjobo‐Hermans

Willems

et al. 2019

Antioxidants & Redox Signaling

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“…S1P production by hypoxia stimulated the glycolytic flux in erythrocytes through the release of a membrane-bound glycolytic enzyme, which is critical for the upregulating of hemoglobin's oxygen release capacity in erythrocytes 26,27 . In addition to the HIF1-regulated S1P metabolism, inhibition of sphingosine kinase 2, the isotype of mitochondrial S1P-producing enzyme, reduced oxidative stress through the suppression of Nrf2 accumulation, SOD2 expression, and mitochondrial respiration 51,52 . However, our data revealed that cP1P did not affect Nrf2 accumulation or SOD2 expression and acetylation.…”

Section: Discussionmentioning

confidence: 99%

O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells

et al. 2019

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O-cyclic phytosphingosine-1-phosphate (cP1P) is a novel chemically synthesized sphingosine metabolite derived from phytosphingosine-1-phosphate. Although structurally similar to sphingosine-1-phosphate (S1P), its biological properties in stem cells remain to be reported. We investigated the effect of cP1P on the therapeutic potential of mesenchymal stem cells (MSCs) and their regulatory mechanism. We found that, under hypoxia, cP1P suppressed MSC mitochondrial dysfunction and apoptosis. Metabolic data revealed that cP1P stimulated glycolysis via the upregulation of glycolysis-related genes. cP1P-induced hypoxia-inducible factor 1 alpha (HIF1α) plays a key role for MSC glycolytic reprogramming and transplantation efficacy. The intracellular calcium-dependent PKCα/mammalian target of the rapamycin (mTOR) signaling pathway triggered by cP1P regulated HIF1α translation via S6K1, which is critical for HIF1 activation. Furthermore, the cP1P-activated mTOR pathway induced bicaudal D homolog 1 expression, leading to HIF1α nuclear translocation. In conclusion, cP1P enhances the therapeutic potential of MSC through mTOR-dependent HIF1α translation and nuclear translocation.

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“…All these signals are candidate targets of potential obesogenic EDCs. Lipids, which role has been considered crucial in many tissues including liver, fat and intestine are accumulated and stored till their use in case of energy needs ( 5 ). Many studies so far have been carried out to reveal the pivotal role of dietary lipid intake as a source of essential fatty acids governing energy balance, food intake, growth, reproduction and health.…”

Section: Introductionmentioning

confidence: 99%

Lipid Metabolism Alteration by Endocrine Disruptors in Animal Models: An Overview

Maradonna

Carnevali

2018

Front. Endocrinol.

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Exposure to potential Endocrine Disrupting Chemicals (EDCs) pose a documented risk to both wildlife and human health. Many studies so far described declining sperm counts, genital malformations, early puberty onset, highlighting the negative impact on reproduction caused by the exposure to many anthropogenic chemicals. In the last years, increasing evidence suggested that these compounds, other than altering reproduction, affect metabolism and induce the onset of obesity and metabolic disorders. According to the “environmental obesogens” hypothesis, evidence exists that exposure to potential EDCs during critical periods when adipocytes are differentiating, and organs are developing, can induce diseases that manifest later in the life. This review summarizes the effects occurring at the hepatic level in different animal models, describing morphological alterations and changes of molecular pathways elicited by the toxicant exposure. Results currently available demonstrated that these chemicals impair normal metabolic processes via interaction with members of the nuclear receptor superfamily, including steroid hormone receptors, thyroid hormone receptors, retinoid X receptors, peroxisome proliferator–activated receptors, liver X receptors, and farnesoid X receptors. In addition, novel results revealed that EDC exposure can either affect circadian rhythms as well as up-regulate the expression of signals belonging to the endocannabinoid system, in both cases leading to a remarkable increase of lipid accumulation. These results warrant further research and increase the interest toward the identification of new mechanisms for EDC metabolic alterations. The last part of this review article condenses recent evidences on the ability of potential EDCs to cause “transgenerational effects” by a single prenatal or early life exposure. On this regard, there is compelling evidence that epigenetic modifications link developmental environmental insults to adult disease susceptibility. This review will contribute to summarize the mechanisms underlying the insurgence of EDC-induced metabolic alterations as well as to build integrated strategies for their better management. In fact, despite the large number of results obtained so far, there is still a great demand for the development of frameworks that can integrate mechanistic and toxicological/epidemiological observations. This would increase legal and governmental institution awareness on this critical environmental issue responsible for negative consequences in both wild species and human health.

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Lipid-mediated signals that regulate mitochondrial biology

Cited by 34 publications

References 49 publications

Mitochondrial Morphofunction in Mammalian Cells

Mitochondrial Morphofunction in Mammalian Cells

O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells

Lipid Metabolism Alteration by Endocrine Disruptors in Animal Models: An Overview

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