Lipophagy: a new player in CNS disorders

Haidar, Mansour; Loix, Melanie; Bogie, Jeroen F. J.; Hendriks, Jerome J. A.

doi:10.1016/j.tem.2021.08.010

Cited by 26 publications

(18 citation statements)

References 89 publications

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“…These dynamic organelles change between periods of growth and consumption through enzymatic hydrolysis mediated by lipases (lipolysis) or selective autophagy (lipophagy) [ 17 ]. The lipolysis process involves several cytoplasmic lipases, including adipose triglyceride lipase (ATGL), hormone-sensitive lipase, and monoacylglycerol lipase, which catalyze hydrolysis of TAG and CE [ 84 ]. Subsequently, lipophagy can target LDs for degradation and release of FFAs and glycerol [ 85 ].…”

Section: Lipid Droplets and Lipid Metabolism At Mamsmentioning

confidence: 99%

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases

Fernandes

Domingues

Moreira

et al. 2023

Biology

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Mitochondria interact with the endoplasmic reticulum (ER) through contacts called mitochondria-associated membranes (MAMs), which control several processes, such as the ER stress response, mitochondrial and ER dynamics, inflammation, apoptosis, and autophagy. MAMs represent an important platform for transport of non-vesicular phospholipids and cholesterol. Therefore, this region is highly enriched in proteins involved in lipid metabolism, including the enzymes that catalyze esterification of cholesterol into cholesteryl esters (CE) and synthesis of triacylglycerols (TAG) from fatty acids (FAs), which are then stored in lipid droplets (LDs). LDs, through contact with other organelles, prevent the toxic consequences of accumulation of unesterified (free) lipids, including lipotoxicity and oxidative stress, and serve as lipid reservoirs that can be used under multiple metabolic and physiological conditions. The LDs break down by autophagy releases of stored lipids for energy production and synthesis of membrane components and other macromolecules. Pathological lipid deposition and autophagy disruption have both been reported to occur in several neurodegenerative diseases, supporting that lipid metabolism alterations are major players in neurodegeneration. In this review, we discuss the current understanding of MAMs structure and function, focusing on their roles in lipid metabolism and the importance of autophagy in LDs metabolism, as well as the changes that occur in neurogenerative diseases.

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Section: Lipid Droplets and Lipid Metabolism At Mamsmentioning

confidence: 99%

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases

Fernandes

Domingues

Moreira

et al. 2023

Biology

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“…LDs can be directly targeted for degradation by lysosomes. Furthermore, the LD-associated protein perilipins can be degraded by CMA, making LDs more susceptible to lipophagy and lipolytic degradation [ 145 ].…”

Section: Lipophagysmentioning

confidence: 99%

Mechanistic Insights into Selective Autophagy Subtypes in Alzheimer’s Disease

Guan

Iyaswamy

Sreenivasmurthy

et al. 2022

IJMS

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Eukaryotic cells possess a plethora of regulatory mechanisms to maintain homeostasis and ensure proper biochemical functionality. Autophagy, a central, conserved self-consuming process of the cell, ensures the timely degradation of damaged cellular components. Several studies have demonstrated the important roles of autophagy activation in mitigating neurodegenerative diseases, especially Alzheimer’s disease (AD). However, surprisingly, activation of macroautophagy has not shown clinical efficacy. Hence, alternative strategies are urgently needed for AD therapy. In recent years, selective autophagy has been reported to be involved in AD pathology, and different subtypes have been identified, such as aggrephagy, mitophagy, reticulophagy, lipophagy, pexophagy, nucleophagy, lysophagy and ribophagy. By clarifying the underlying mechanisms governing these various subtypes, we may come to understand how to control autophagy to treat AD. In this review, we summarize the latest findings concerning the role of selective autophagy in the pathogenesis of AD. The evidence overwhelmingly suggests that selective autophagy is an active mechanism in AD pathology, and that regulating selective autophagy would be an effective strategy for controlling this pathogenesis.

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“…Diacylglycerol can be further hydrolyzed to produce additional free fatty acids by the sequential action of Hormone Sensitive Lipase (HSL) and Monoacylglycerol Lipase (MAGL). During lipophagy, neutral lipids are degraded by a selective form of autophagy in which LDs are engulfed by autophagosomes, which then fuse with acidic lysosomes so that TAGs and CEs can then be degraded by the lysosomal acidic lipases ( Singh et al, 2009 ; Martinez-Lopez and Singh, 2015 ; Haidar et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…From as far back as Alois Alzheimer’s 1907 description of glial “adipose saccules”, numerous correlations have been made between LD accumulation in the brain and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. The links between lipid metabolism, LDs and these neurodegenerative diseases have been discussed in detail in a number of recent reviews ( Hamilton and Fernandes, 2018 ; Pennetta and Welte, 2018 ; Farmer et al, 2020 ; Haidar et al, 2021 ; Tadepalle and Rugarli, 2021 ; Teixeira et al, 2021 ). For some hereditary neurodegenerative conditions, causal links have been made to mutations in genes encoding proteins regulating LD biogenesis or turnover.…”

Section: Introductionmentioning

confidence: 99%

Functions of Stress-Induced Lipid Droplets in the Nervous System

Islimye

Girard

Gould

2022

Front. Cell Dev. Biol.

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Lipid droplets are highly dynamic intracellular organelles that store neutral lipids such as cholesteryl esters and triacylglycerols. They have recently emerged as key stress response components in many different cell types. Lipid droplets in the nervous system are mostly observed in vivo in glia, ependymal cells and microglia. They tend to become more numerous in these cell types and can also form in neurons as a consequence of ageing or stresses involving redox imbalance and lipotoxicity. Abundant lipid droplets are also a characteristic feature of several neurodegenerative diseases. In this minireview, we take a cell-type perspective on recent advances in our understanding of lipid droplet metabolism in glia, neurons and neural stem cells during health and disease. We highlight that a given lipid droplet subfunction, such as triacylglycerol lipolysis, can be physiologically beneficial or harmful to the functions of the nervous system depending upon cellular context. The mechanistic understanding of context-dependent lipid droplet functions in the nervous system is progressing apace, aided by new technologies for probing the lipid droplet proteome and lipidome with single-cell type precision.

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Lipophagy: a new player in CNS disorders

Cited by 26 publications

References 89 publications

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases

Mechanistic Insights into Selective Autophagy Subtypes in Alzheimer’s Disease

Functions of Stress-Induced Lipid Droplets in the Nervous System

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