Spatial compartmentalization of lipid droplet biogenesis

Henne, Mike; Goodman, Joel M.; Hariri, Hanaa

doi:10.1016/j.bbalip.2019.07.008

Cited by 43 publications

(43 citation statements)

References 138 publications

(168 reference statements)

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“…These lipids and proteins can traffic between lipid droplets and endoplasmic reticulum, and FATP1 may have a role in facilitating lipid droplet transport at this interface. 41 - 44 The origin and significance of nuclear lipid droplets is uncertain, but the inner nuclear membrane can metabolize lipids and regulate transcription in response to lipid availability. 45 , 46 Recent understanding of the mechanisms of interaction between chromatin and lipids suggests that small lipid molecules can regulate main nuclear functions.…”

Section: Discussionmentioning

confidence: 99%

Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

André

Pinto

Silva

et al. 2021

Breast Cancer�(Auckl)

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Background: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients’ advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. Objective: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. Material and methods: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. Results: Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. Conclusions: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

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Section: Discussionmentioning

confidence: 99%

Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

André

Pinto

Silva

et al. 2021

Breast Cancer�(Auckl)

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“…Cytoplasmic lipid droplets in RA T cells are not only an indicator of cellular stress. Rather, the availability of neutral lipids stored as cytoplasmic lipid droplets is a necessary element in a cell building program; for example, during times of effector T cell differentiation. Thus, favoring lipogenesis over lipolysis supports the RA T cell's switch from catabolism to anabolism and from ATP production to building cellular offspring.…”

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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“…While the 3-dimensional structure of PLIN2 is not known, based on homology with the structure of perilipin 3 (10), it is theorized that the Pro251 substitution causes a tertiary change in PLIN2, which may decrease hormone sensitive lipase (11) or adipose triglyceride lipase (12) docking to PLIN2 on the LD surface. Further research is needed to delineate if the Pro251 variant impacts aspects of LD biology outside of lipolysis including biogenesis in the endoplasmic reticulum (13), fusion (14) and autophagy (12) summarized in figure 2.…”

Section: Discussionmentioning

confidence: 99%

A single nucleotide polymorphism of PLIN2 is associated with nonalcoholic steatohepatitis and causes phenotypic changes in hepatocyte lipid droplets

Faulkner

White

Jophlin

2019

Preprint

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24Perilipin 2 (PLIN2) is a lipid droplet-associated protein which regulates cellular lipid 25 storage and is highly expressed in the liver. Previous studies of a missense single 26 nucleotide polymorphism (SNP) in PLIN2, Ser251Pro, (i.e. rs3556875) have shown this 27 SNP to cause decreased lipolysis and increased intracellular lipid accumulation. To 28 explore if this SNP is associated with nonalcoholic steatohepatitis (NASH), we 29 genotyped 116 adults with NASH and 67 age-and gender-matched controls. 30 rs3556875 was significantly associated with NASH with an allelic odds ratio of 2.98 (95% 31 confidence interval 1.12 -7.31, p=0.02) and in a dominant inheritance model. In an in vitro 32 model of hepatic steatosis, expression of the Pro251 variant protein led to phenotypic 33 changes in intracellular lipid droplets, yielding smaller diameter and up to 7 fold more lipid 34 droplets per cell when compared to wild type PLIN2. In conclusion, the Ser251Pro SNP of PLIN2 35 may convey risk for NASH and causes phenotypic changes in hepatocyte lipid droplets. 36 37 KEYWORDS 38 Non-alcoholic steatohepatitis, perilipin 2, hepatic steatosis, lipid droplet, single 39 nucleotide polymorphism 40 41

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Spatial compartmentalization of lipid droplet biogenesis

Cited by 43 publications

References 138 publications

Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

Immunometabolism in the development of rheumatoid arthritis

A single nucleotide polymorphism of PLIN2 is associated with nonalcoholic steatohepatitis and causes phenotypic changes in hepatocyte lipid droplets

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