LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs

Etxaniz, Asier; Varela, Yaiza R.; Hervás, Javier H.; Montes, L. Ruth; Goñi, Félix M.; Alonso, Alicia

doi:10.1080/15548627.2022.2062111

Cited by 38 publications

(25 citation statements)

References 65 publications

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“…2c, g), thus parting with the rest of the LC3 subfamily. LC3C equally failed to follow the general trends of the LC3 subfamily in previous studies on cardiolipin-mediated mitophagy [20].…”

Section: Discussionmentioning

confidence: 57%

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Effect of ATG12–ATG5-ATG16L1 autophagy E3 complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

Etxaniz

Varela

Lázaro

et al. 2022

Preprint

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In macroautophagy, the autophagosome (AP) engulfs portions of cytoplasm to allow their lysosomal degradation. AP formation in humans requires the concerted action of the ATG12 and LC3/GABARAP conjugation systems. The ATG12–ATG5-ATG16L1 (E3) complex acts as a ubiquitin-like E3 ligase enzyme, promoting LC3/GABARAP protein anchoring to the AP membrane. The role of the various proteins in the AP expansion process is still unclear, in part because there are no studies comparing LC3/GABARAP-family member roles under the same conditions, and also because the full human E3 complex was only recently available. In the present study, the lipidation of six members of the LC3/GABARAP family has been reconstituted in the presence and absence of E3, and the mechanisms by which E3 and LC3/GABARAP proteins participate in vesicle tethering and fusion have been investigated. In the absence of E3, GABARAP and GABARAPL1 showed the highest activities. Differences found within LC3/GABARAP proteins suggest the existence of a lipidation threshold, lower for the GABARAP subfamily, as a requisite for tethering and inter-vesicular lipid mixing. E3 increases and speeds up lipidation and LC3/GABARAP-promoted tethering. However E3 hampers LC3/GABARAP capacity to induce inter-vesicular lipid mixing or subsequent fusion, presumably through formation of a rigid scaffold on the vesicle surface. Our results suggest a model of AP expansion in which the growing regions would be areas where the LC3/GABARAP proteins involved should be susceptible to lipidation in the absence of E3, or else a regulatory mechanism would allow vesicle incorporation and phagophore growth when E3 is present.

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“…2c, g), thus parting with the rest of the LC3 subfamily. LC3C equally failed to follow the general trends of the LC3 subfamily in previous studies on cardiolipin-mediated mitophagy [20].…”

Section: Discussionmentioning

confidence: 57%

“…Once attached to the membrane, LC3/GABARAP proteins are able to interact with receptors for the selective recognition of the cargo to be degraded [18][19][20]. In addition, they are also involved in autophagosomal membrane expansion, closure, and fusion with lysosomes [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Effect of ATG12–ATG5-ATG16L1 autophagy E3 complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

Etxaniz

Varela

Lázaro

et al. 2022

Preprint

Self Cite

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“…Selective CL oxidation initiates three hours after TBI injury in the TBI model. In mammalian cells, externalization of CL to OMM serves as an elimination signal to promote mitophagy by directly interacting with LC3 [85].…”

Section: Receptor-mediated Mitophagy In Tbimentioning

confidence: 99%

Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials

Luan

Jiang

Luan

et al. 2023

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI), a kind of external trauma-induced brain function alteration, has posed a financial burden on the public health system. TBI pathogenesis involves a complicated set of events, including primary and secondary injuries that can cause mitochondrial damage. Mitophagy, a process in which defective mitochondria are specifically degraded, segregates and degrades defective mitochondria allowing a healthier mitochondrial network. Mitophagy ensures that mitochondria remain healthy during TBI, determining whether neurons live or die. Mitophagy acts as a critical regulator in maintaining neuronal survival and healthy. This review will discuss the TBI pathophysiology and the consequences of the damage it causes to mitochondria. This review article will explore the mitophagy process, its key factors, and pathways and reveal the role of mitophagy in TBI. Mitophagy will be further recognized as a therapeutic approach in TBI. This review will offer new insights into mitophagy’s role in TBI progression.

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“…The mitochondrial unique phospholipid cardiolipin (CL), which is predominantly found in the inner mitochondrial membrane (IMM) [ 106 ], is crucial for biophysical properties of mitochondrial membranes, where it modulates energy production and participates in inflammation, mitophagy and apoptosis [ 107 , 108 , 109 , 110 , 111 ]. Intriguingly, the structural disruptions that accompany late stage regulated cell death generate mitochondrial fragments containing CL in the extracellular microenvironment, where CL promotes increased expression of MHC class I-like molecule CD1d on antigen presenting cells and results in the activation of a cardiolipin-specific population of T cells [ 112 ].…”

Section: Mitochondrial Regulation Of Cell Deathmentioning

confidence: 99%

Mitochondrial Contribution to Inflammation in Diabetic Kidney Disease

Mitrofanova

Fontanella

Burke

et al. 2022

Cells

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Diabetes is the leading cause of chronic kidney disease worldwide. Despite the burden, the factors contributing to the development and progression of diabetic kidney disease (DKD) remain to be fully elucidated. In recent years, increasing evidence suggests that mitochondrial dysfunction is a pathological mediator in DKD as the kidney is a highly metabolic organ rich in mitochondria. Furthermore, low grade chronic inflammation also contributes to the progression of DKD, and several inflammatory biomarkers have been reported as prognostic markers to risk-stratify patients for disease progression and all-cause mortality. Interestingly, the term “sterile inflammation” appears to be used in the context of DKD describing the development of intracellular inflammation in the absence of bacterial or viral pathogens. Therefore, a link between mitochondrial dysfunction and inflammation in DKD exists and is a hot topic in both basic research and clinical investigations. This review summarizes how mitochondria contribute to sterile inflammation in renal cells in DKD.

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LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs

Cited by 38 publications

References 65 publications

Effect of ATG12–ATG5-ATG16L1 autophagy E3 complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

Effect of ATG12–ATG5-ATG16L1 autophagy E3 complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion

Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials

Mitochondrial Contribution to Inflammation in Diabetic Kidney Disease

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