LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy

Omrane, Mohyeddine; M’Barek, Kalthoum Ben; Santinho, Alexandre; Nguyen, Nathan; Nag, Shanta; Melia, Thomas J.; Thiam, Abdou Rachid

doi:10.1016/j.devcel.2023.05.009

Cited by 11 publications

(3 citation statements)

References 75 publications

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“…The versatility of GERVs can hence enable further highlighting of biophysical properties and mechanisms of LD biogenesis. Other GOVs may likewise serve to reproduce and study the functionalities of their corresponding organelles 52 .…”

Section: Resultsmentioning

confidence: 99%

Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity

Santinho,

Carpentier,

Lopes Sampaio

et al. 2024

Nat Commun

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Tools for accessing and studying organelles remain underdeveloped. Here, we present a method by which giant organelle vesicles (GOVs) are generated by submitting cells to a hypotonic medium followed by plasma membrane breakage. By this means, GOVs ranging from 3 to over 10 µm become available for micromanipulation. GOVs are made from organelles such as the endoplasmic reticulum, endosomes, lysosomes and mitochondria, or in contact with one another such as giant mitochondria-associated ER membrane vesicles. We measure the mechanical properties of each organelle-derived GOV and find that they have distinct properties. In GOVs procured from Cos7 cells, for example, bending rigidities tend to increase from the endoplasmic reticulum to the plasma membrane. We also found that the mechanical properties of giant endoplasmic reticulum vesicles (GERVs) vary depending on their interactions with other organelles or the metabolic state of the cell. Lastly, we demonstrate GERVs’ biochemical activity through their capacity to synthesize triglycerides and assemble lipid droplets. These findings underscore the potential of GOVs as valuable tools for studying the biophysics and biology of organelles.

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Section: Resultsmentioning

confidence: 99%

Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity

Santinho,

Carpentier,

Lopes Sampaio

et al. 2024

Nat Commun

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“…Lipid droplets (LDs) were prepared with Triolein as oil-phase according to available protocols 51,54 . A lipid solution doped with 0.001 mol% Rh-PE in methanol was dried in microcentrifuge tubes under a nitrogen stream.…”

Section: Lipid Droplet Preparation (Oil-water Monolayers)mentioning

confidence: 99%

A comparison of lipid diffusive dynamics in monolayers and bilayers in the context of interleaflet coupling

Mandal,

Brandt,

Tempra

et al. 2024

Preprint

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Cellular membranes are composed of lipids typically organized in a double-leaflet structure. Interactions between these two leaflets - often referred to as interleaflet coupling - play a crucial role in various cellular processes. Despite extensive study, the mechanisms governing such interactions remain incompletely understood. Here, we investigate the effects of interleaflet coupling from a specific point of view, i.e. by comparing diffusive dynamics in bilayers and monolayers, focusing on potential lipid-specific interactions between opposing leaflets. Through quantitative fluorescence microscopy techniques, we characterize lipid diffusion and mean molecular area in monolayers and bilayers composed of different lipids. Our results suggest that the observed decrease in bilayer lipid diffusion compared to monolayers depends on lipid identity. Furthermore, our analysis suggests that lipid acyl chain structure and spatial configuration at the bilayer may strongly influence interleaflet interactions and dynamics in bilayers. These findings provide insights into the role of lipid structure in mediating interleaflet coupling and underscore the need for further experimental investigations to elucidate the underlying mechanisms.

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“…Whereas LC3B continues to be used to monitor autophagy, it has become evident that it can be present on membranes other than autophagosomes (77). Thus far, mammalian membranes that have been reported to be atg8ylated (covalently modified by mATG8s, typically reported as LC3B but not limited to this mATG8) include: conventional phagosomes harboring pathogens or microbial products (78)(79)(80)(81), various types of stressed or signaling endosomal compartments (12-14, 79, 82), lysosomes (48, 66, 83-86), exocytic compartments releasing exosomes (52, 87), ER during its piecemeal ESCRT-dependent lysosomal degradation (88), and lipid droplets (89). Of note, the delimiting membrane of lipid droplets modified by LC3B is not even a full lipid bilayer but a monolayer of phospholipids (89).…”

Section: Manifestations Of Membrane Atg Ylationmentioning

confidence: 99%

Atg8ylation as a host-protective mechanism against Mycobacterium tuberculosis

Deretic

2023

Front. Tuberc

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Nearly two decades have passed since the first report on autophagy acting as a cell-autonomous defense against Mycobacterium tuberculosis. This helped usher a new area of research within the field of host-pathogen interactions and led to the recognition of autophagy as an immunological mechanism. Interest grew in the fundamental mechanisms of antimicrobial autophagy and in the prophylactic and therapeutic potential for tuberculosis. However, puzzling in vivo data have begun to emerge in murine models of M. tuberculosis infection. The control of infection in mice affirmed the effects of certain autophagy genes, specifically ATG5, but not of other ATGs. Recent studies with a more complete inactivation of ATG genes now show that multiple ATG genes are indeed necessary for protection against M. tuberculosis. These particular ATG genes are involved in the process of membrane atg8ylation. Atg8ylation in mammalian cells is a broad response to membrane stress, damage and remodeling of which canonical autophagy is one of the multiple downstream outputs. The current developments clarify the controversies and open new avenues for both fundamental and translational studies.

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LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy

Cited by 11 publications

References 75 publications

Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity

Giant organelle vesicles to uncover intracellular membrane mechanics and plasticity

A comparison of lipid diffusive dynamics in monolayers and bilayers in the context of interleaflet coupling

Atg8ylation as a host-protective mechanism against Mycobacterium tuberculosis

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