Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans

Collier, Jack J; Guissart, Claire; Oláhová, Monika; Sasorith, Souphatta; Piron‐Prunier, Florence; Suomi, Fumi; Zhang, David; Martínez–López, Nuria; Leboucq, Nicolas; Bahr, Angela; Azzarello-Burri, Silvia; Reich, Selina; Schöls, Lüdger; Polvikoski, Tuomo; Meyer, Pierre; Larrieu, Lise; Schaefer, Andrew M.; Alsaif, Hessa S.; Alyamani, Suad; Züchner, Stephan; Barbosa, Inês A.; Deshpande, Charu; Pyle, Angela; Rauch, Anita; Synofzik, Matthis; Alkuraya, Fowzan S.; Rivier, François; Ryten, Mina; McFarland, Robert; Delahodde, Agnès; McWilliams, Thomas G.; Kœnig, M.; Taylor, Robert W.

doi:10.1056/nejmoa1915722

Cited by 107 publications

(58 citation statements)

References 40 publications

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“…Importantly, plasmid mediated-ATG7 overexpression for 14 days in aged skeletal muscles restored autophagy, ameliorated the integrity of neuromuscular junctions, and increased myofiber size [ 102 ]. In humans, mutations in ATG7 cause neurodevelopmental disorders involving neurologic, muscular, and endocrine hypofunction [ 109 ]. It was also reported that p62/SQSTM1 (sequestosome-1) accumulates in aged skeletal muscles, suggesting that a decline in autophagy may contribute to sarcopenia [ 110 ].…”

Section: The Role Of Autophagy In Skeletal Muscle Health and Agingmentioning

confidence: 99%

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Leduc‐Gaudet

Hussain

Barreiro

et al. 2021

IJMS

140

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The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range of cellular processes, including energy supply, Ca2+ homeostasis, retrograde signaling, cell death, and many others. All mitochondria-containing cells, including skeletal muscle cells, dispose of several pathways to maintain mitochondrial health, including mitochondrial biogenesis, mitochondrial-derived vesicles, mitochondrial dynamics (fusion and fission process shaping mitochondrial morphology), and mitophagy—the process in charge of the removal of mitochondria though autophagy. The loss of skeletal muscle mass (atrophy) is a major health problem worldwide, especially in older people. Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia. There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contributes to the development of sarcopenia. Impairments in mitochondrial dynamics and mitophagy were recently proposed to contribute to sarcopenia. This review summarizes the current state of knowledge on the role played by mitochondrial dynamics and mitophagy in skeletal muscle health and in the development of sarcopenia. We also highlight recent studies showing that enhancing mitophagy in skeletal muscle is a promising therapeutic target to prevent or even treat skeletal muscle dysfunction in the elderly.

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Section: The Role Of Autophagy In Skeletal Muscle Health and Agingmentioning

confidence: 99%

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Leduc‐Gaudet

Hussain

Barreiro

et al. 2021

IJMS

140

View full text Add to dashboard Cite

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“…Furthermore, the Atg8-PE has also been found to be important for the closure of isolation membranes to form sealed autophagosomes, indicating that Atg8-PE may possess membrane fission function in addition to its role in membrane fusion [46,51]. However, studies also showed that autophagosomes can correctly seal in the absence of Atg8-PE, which does not support the role of Atg8-PE in the closure of autophagosomal membranes [52][53][54]. Recently, several studies have shown that the endosomal sorting complexes required for transport (ESCRT) machinery plays a pivotal role in the closure of autophagosomal membranes [55][56][57][58].…”

Section: Autophagosome Formation and Atg8/lc3 Scaffolds As Platforms For Receptor Cargo Recruitmentmentioning

confidence: 95%

Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates

Shen

Wang

2021

Cells

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The selective targeting and disposal of solid protein aggregates are essential for cells to maintain protein homoeostasis. Autophagy receptors including p62, NBR1, Cue5/TOLLIP (CUET), and Tax1-binding protein 1 (TAX1BP1) proteins function in selective autophagy by targeting ubiquitinated aggregates through ubiquitin-binding domains. Here, we summarize previous beliefs and recent findings on selective receptors in aggregate autophagy. Since there are many reviews on selective autophagy receptors, we focus on their oligomerization, which enables receptors to function as pathway determinants and promotes phase separation.

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“…Mutation in ATG5 [82] or ATG7 leads to neurodegeneration [83], because inhibited or inefficient autophagy results in the accumulation of ubiquitinated protein aggregates within neurons [84,85]. Although cells with loss of ATG7 are regarded as "autophagydeficient", autophagosomes (some containing mitochondria) were present in muscle cells and fibroblasts derived from the patients with recessive variants in ATG7.…”

Section: The Role Of Alternative Autophagymentioning

confidence: 99%

“…Although cells with loss of ATG7 are regarded as "autophagydeficient", autophagosomes (some containing mitochondria) were present in muscle cells and fibroblasts derived from the patients with recessive variants in ATG7. This indicates that a lack of ATG does not completely stall canonical autophagy or that the observed autophagosomes were generated via alternative autophagy [83]. In this case, alternative autophagy (activated during chronic inhibition of canonical autophagy) could be a mechanism maintaining homeostasis [86].…”

Section: The Role Of Alternative Autophagymentioning

confidence: 99%

“…In this case, alternative autophagy (activated during chronic inhibition of canonical autophagy) could be a mechanism maintaining homeostasis [86]. Indeed, patients with biallelic deleterious ATG7 variants have similar life expectancy to the general population [83]. However, this alternative autophagy may prompt further cellular damage (including nuclear breakdown) and lead to cell atrophy and finally degeneration [86].…”

Section: The Role Of Alternative Autophagymentioning

confidence: 99%

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The Secrets of Alternative Autophagy

Urbańska

Orzechowski

2021

Cells

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For many years, it was thought that ATG5 and ATG7 played a pivotal role in autophagy, and that the knockdown of one of these genes would result in its inhibition. However, cells with ATG5 or ATG7 depletion still generate autophagic vacuoles with mainly trans-Golgi-originated isolation membranes and do not die. This indicates that autophagy can occur via ATG5/ATG7-independent alternative autophagy. Its molecular mechanism differs from that of the canonical pathway, including inter alia the phosphorylation of ULK1, and lack of LC3 modifications. As the alternative autophagy pathway has only recently been described, little is known of its precise role; however, a considerable body of evidence suggests that alternative autophagy participates in mitochondrion removal. This review summarizes the latest progress made in research on alternative autophagy and describes its possible molecular mechanism, roles and methods of detection, and possible modulators. There is a need for further research focused on types of autophagy, as this can elucidate the functioning of various cell types and the pathogenesis of human and animal diseases.

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Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans

Cited by 107 publications

References 40 publications

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging

Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates

The Secrets of Alternative Autophagy

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