And three’s a party: lysosomes, lipid droplets, and the ER in lipid trafficking and cell homeostasis

Henne, Mike

doi:10.1016/j.ceb.2019.02.011

Cited by 40 publications

(26 citation statements)

References 67 publications

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“…This engineering work ended up with the generation of a class of sensors tested for their ability to detect simultaneous organelle interactions occurring between the ER-mitochondria and the ER-PM (namely the SPLICS S/L -P2A ER-MT-PM ) and occurring between PO-Mitochondria and PO-ER (SPLICS S/L -P2A PO-MT-ER ) in different spectral variants making them unique tools to explore the nature of these organelle interfaces under different physiological and pathological conditions in vitro and in vivo. Eventually this approach can be extended to explore additional tripartite contact sites 35,36 . One final point deserves mention: organelles are dynamic; thus, organelle contact sites must also be dynamic.…”

Section: Discussionmentioning

confidence: 99%

An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo

et al. 2020

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Membrane contact sites between virtually any known organelle have been documented and, in the last decades, their study received momentum due to their importance for fundamental activities of the cell and for the subtle comprehension of many human diseases. The lack of tools to finely image inter-organelle proximity hindered our understanding on how these subcellular communication hubs mediate and regulate cell homeostasis. We develop an improved and expanded palette of split-GFP-based contact site sensors (SPLICS) for the detection of single and multiple organelle contact sites within a scalable distance range. We demonstrate their flexibility under physiological conditions and in living organisms.

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Section: Discussionmentioning

confidence: 99%

An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo

et al. 2020

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“…29 Lipid metabolism is important for muscle contraction, and the number of lipid droplets (LDs) in tissue depends on lipid utilization and the activity of enzymes and co-activators required to synthesize and degrade LDs. 30,31 The expression of PLIN4 is mostly limited to adipocytes, brain, skeletal muscle, et cetera , 32 and its expression in the synovium of rotator cuff injury is significantly up-regulated compared with normal ( p < 0.05), suggesting that a large amount of lipid is produced in the synovium of shoulder joint in patients with rotator cuff injury, which is closely related to fat infiltration. Its expression in synovium of patients with rotator cuff injury was significantly up-regulated compared with the control group ( p < 0.05), which suggests that PLIN4 is closely related to fat infiltration.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals rotator cuff injury caused by oxidative stress

Yuan

Qian

et al. 2021

Therapeutic Advances in Chronic Disease

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Background and aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics. Methods: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins. Results: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 ( p = 0.011), PLIN4 ( p = 0.017), HYOU1 ( p = 0.002) and CLIC1 ( p = 0.007) were closely related to oxidative stress and chronic inflammation. Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism.

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“…Under physiologic conditions, cells utilize lipid droplets as a rapidly accessible source of fatty acids needed during periods of starvation. Recent work has identified lipid droplets as a sink for lipids released by autophagic breakdown of membranous organelles when cells are entering periods of prolong nutrient deprivation . Thus, lipid droplets may predominantly be a sign of cellular stress and serve as a storage organelle to avoid lipotoxicity, especially derived from acylcarnitines, that threaten integrity of mitochondrial membranes.…”

Section: Ra T Cells Favor Lipogenesis and Accumulate Cytoplasmic Lipimentioning

confidence: 99%

Immunometabolism in the development of rheumatoid arthritis

Weyand

Goronzy

2020

Immunological Reviews

117

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In rheumatoid arthritis (RA), breakdown of self‐tolerance and onset of clinical disease are separated in time and space, supporting a multi‐hit model in which emergence of autoreactive T cells is a pinnacle pathogenic event. Determining factors in T cell differentiation and survival include antigen recognition, but also the metabolic machinery that provides energy and biosynthetic molecules for cell building. Studies in patients with RA have yielded a disease‐specific metabolic signature, which enables naive CD4 T cells to differentiate into pro‐inflammatory helper T cells that are prone to invade into tissue and elicit inflammation through immunogenic cell death. A typifying property of RA CD4 T cells is the shunting of glucose away from glycolytic breakdown and mitochondrial processing toward the pentose phosphate pathway, favoring anabolic over catabolic reactions. Key defects have been localized to the mitochondria and the lysosome; including instability of mitochondrial DNA due to the lack of the DNA repair nuclease MRE11A and inefficient lysosomal tethering of AMPK due to deficiency of N‐myristoyltransferase 1 (NMT1). The molecular taxonomy of the metabolically reprogrammed RA T cells includes glycolytic enzymes (glucose‐6‐phosphate dehydrogenase, phosphofructokinase), DNA repair molecules (MRE11A, ATM), regulators of protein trafficking (NMT1), and the membrane adapter protein TSK5. As the mechanisms determining abnormal T cell behavior in RA are unraveled, opportunities will emerge to interject autoimmune T cells by targeting their metabolic checkpoints.

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And three’s a party: lysosomes, lipid droplets, and the ER in lipid trafficking and cell homeostasis

Cited by 40 publications

References 67 publications

An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo

An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo

Proteomic analysis reveals rotator cuff injury caused by oxidative stress

Immunometabolism in the development of rheumatoid arthritis

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