Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains

Rienzo, Martina Di; Antonioli, Manuela; Fusco, Carmela; Liu, Y.; Mari, Muriel; Orhon, Idil; Refolo, Giulia; Germani, Federico; Corazzari, Marco; Romagnoli, Alessandra; Ciccosanti, Fabiola; Mandriani, Barbara; Pellico, Maria Teresa; Torre, R. De La; Ding, Hao; Dentice, Monica; Neri, Marcella; Ferlini, Alessandra; Reggiori, Fulvio; Kulesz‐Martin, Molly; Piacentini, Mauro; Merla, Giuseppe; Fimia, Gian María

doi:10.1126/sciadv.aau8857

Cited by 79 publications

(73 citation statements)

References 65 publications

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“…Further studies with TRIM5 showed that it also interacted with ATG14L1 and AMBRA1, both proteins that interact with the Beclin 1 complex. Additional studies have broadened the list of TRIMs that interact with the ULK1 and/or Beclin 1 complexes to include TRIMs 13, 16, 20, 21, 28, 32, and 50 (Yang et al, 2013;Kimura et al, 2015;Chauhan et al, 2016;Fusco et al, 2018;Di Rienzo et al, 2019;Ji et al, 2019). However, the finding that a TRIM interacts with these upstream regulators of autophagy does not necessarily prove that it acts to promote autophagy, as exemplified by TRIM17 which binds to ULK1 and Beclin 1 yet was found to inhibit autophagosome formation (Mandell et al, 2014;Mandell et al, 2016).…”

Section: Actions Of Trims On Autophagy Machinerymentioning

confidence: 99%

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

2020

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Autophagy is a cellular degradative process that has multiple important actions in cancer. Autophagy modulation is under consideration as a promising new approach to cancer therapy. However, complete autophagy dysregulation is likely to have substantial undesirable side effects. Thus, more targeted approaches to autophagy modulation may prove clinically beneficial. One potential avenue to achieving this goal is to focus on the actions of tripartite motif-containing protein family members (TRIMs). TRIMs have key roles in an array of cellular processes, and their dysregulation has been extensively linked to cancer risk and prognosis. As detailed here, emerging data shows that TRIMs can play important yet context-dependent roles in controlling autophagy and in the selective targeting of autophagic substrates. This review covers how the autophagyrelated actions of TRIM proteins contribute to cancer and the possibility of targeting TRIMdirected autophagy in cancer therapy.

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Section: Actions Of Trims On Autophagy Machinerymentioning

confidence: 99%

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

2020

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“…Knockdown cells were produced by transfecting Hek293T packaging cells with the lentiviral pLKO vector together with the Pax2 (pMDLg/p and pRSV-Rev plasmids) and ENV (VSV-G) plasmids [17]. The pLKO vector containing a shRNA for Prdx6 or for GFP (used as control), were purchased from Sigma Aldrich, Saint Louis, MO, USA.…”

Section: Stably Silenced Murine Myoblast C2c12 Cell Linementioning

confidence: 99%

Prdx6 Plays a Main Role in the Crosstalk between Aging and Metabolic Sarcopenia

et al. 2020

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With the increase in average life expectancy, several individuals are affected by age-associated non-communicable chronic diseases (NCDs). The presence of NCDs, such as type 2 diabetes mellitus (T2DM), leads to the reduction in skeletal muscle mass, a pathological condition defined as sarcopenia. A key factor linking sarcopenia with cellular senescence and diabetes mellitus (DM) is oxidative stress. We previously reported as the absence of Peroxiredoxin 6 (Prdx6), an antioxidant enzyme implicated in maintaining intracellular redox homeostasis, induces an early-stage of T2DM. In the present study we sought to understand the role of Prdx6 in the crosstalk between aging and diabetic sarcopenia, by using Prdx6 knockout (Prdx6-/-) mice. Absence of Prdx6 reduced telomeres length and Sirtuin1 (SIRT1) nuclear localization. An increase in Sa-β-Gal activity and p53-p21 pro-aging pathway were also evident. An impairment in IGF-1 (Insulin-like Groth Factor-1)/Akt-1/mTOR pathway leading to a relative increase in Forkhead Box O1 (FOXO1) nuclear localization and in a decrease of muscle differentiation as per lower levels of myoblast determination protein 1 (MyoD) was observed. Muscle atrophy was also present in Prdx6-/- mice by the increase in Muscle RING finger 1 (MuRF1) levels and proteins ubiquitination associated to a reduction in muscle strength. The present study, innovatively, highlights a fundamental role of Prdx6, in the crosstalk between aging, sarcopenia, and DM.

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“…This is particularly important under nutrient-deprived or stress conditions to maintain adequate energy production. Recent studies have shown that basal autophagy is crucial for the maintenance of muscle physiology, and that a maladaptive autophagy is implicated in various muscle diseases, including muscular dystrophy, sarcopenia, and myofibril degeneration [31,66,[82][83][84].…”

Section: Musclementioning

confidence: 99%

The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention

Chung

2019

Nutrients

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Autophagy is an important housekeeping process that maintains a proper cellular homeostasis under normal physiologic and/or pathologic conditions. It is responsible for the disposal and recycling of metabolic macromolecules and damaged organelles through broad lysosomal degradation processes. Under stress conditions, including nutrient deficiency, autophagy is substantially activated to maintain proper cell function and promote cell survival. Altered autophagy processes have been reported in various aging studies, and a dysregulated autophagy is associated with various age-associated diseases. Calorie restriction (CR) is regarded as the gold standard for many aging intervention methods. Although it is clear that CR has diverse effects in counteracting aging process, the exact mechanisms by which it modulates those processes are still controversial. Recent advances in CR research have suggested that the activation of autophagy is linked to the observed beneficial anti-aging effects. Evidence showed that CR induced a robust autophagy response in various metabolic tissues, and that the inhibition of autophagy attenuated the anti-aging effects of CR. The mechanisms by which CR modulates the complex process of autophagy have been investigated in depth. In this review, several major advances related to CR’s anti-aging mechanisms and anti-aging mimetics will be discussed, focusing on the modification of the autophagy response.

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Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains

Cited by 79 publications

References 65 publications

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

Prdx6 Plays a Main Role in the Crosstalk between Aging and Metabolic Sarcopenia

The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention

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