Autophagy in major human diseases

Klionsky, Daniel J.; Petroni, Giulia; Amaravadi, Ravi K.; Baehrecke, Eric H.; Ballabio, Andrea; Boya, Patricia; Pedro, José Manuel Bravo-San; Cadwell, Ken; Cecconi, Francesco; Choi, Augustine M.K.; Choi, Mary E.; Chu, Charleen T.; Codogno, Patrice; Colombo, María Isabel; Cuervo, Ana María; Deretić, Vojo; Đikić, Ivan; Elazar, Zvulun; Eskelinen, Eeva‐Liisa; Fimia, Gian María; Gewirtz, David A.; Green, Douglas R.; Hansen, Malene; Jäättelä, Marja; Johansen, Terje; Juhász, Gábor; Karantza, Vassiliki; Kraft, Claudine; Kroemer, Guido; Ktistakis, Nicholas T.; Kumar, Sharad; López-Otı́n, Carlos; Macleod, Kay F.; Madeo, Frank; Martinez, Jennifer; Meléndez, Alicia; Mizushima, Noboru; Münz, Christian; Penninger, Josef; Perera, Rushika M.; Piacentini, Mauro; Reggiori, Fulvio; Rubinsztein, David C.; Ryan, Kevin M.; Sadoshima, Junichi; Santambrogio, Laura; Scorrano, Luca; Simon, Hans Uwe; Simon, Anna Katharina; Simonsen, Anne; Stolz, Alexandra; Tavernarakis, Nektarios; Tooze, Sharon A.; Yoshimori, Tamotsu; Yuan, Junying; Yue, Zhenyu; Zhong, Qing; Galluzzi, Lorenzo; Pietrocola, Federico

doi:10.15252/embj.2021108863

Cited by 924 publications

(572 citation statements)

References 798 publications

(1,079 reference statements)

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“…Moreover, autophagic response may be connected with differences in the signaling pathways, which use different ATGs [71]; as mentioned, ATG conjugation deficiency slows down autophagic activity [43]. Importantly, cells organized into tissues have higher sensitivity to losing autophagy competence due to their quiescence/postmitotic state [72]. It can also explain the contradictory results obtained for starvation as an alternative autophagy trigger.…”

Section: The Modulators Of Alternative Autophagymentioning

confidence: 99%

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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Section: The Modulators Of Alternative Autophagymentioning

confidence: 99%

The Secrets of Alternative Autophagy

Urbańska

Orzechowski

2021

Cells

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“…Of note, maintaining the delicate balance between the survival and the death of a cell is a key role for the process of autophagy, which has been studied profoundly in last decades [ 38 ]. In this respect, many efforts have been made to identify the autophagic machines, the functional targets and the pathophysiological roles of autophagy in different diseases, including neurodegenerative disorders, retinal defects, metabolic impairments and muscle-related pathologies [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is well established that autophagy can inhibit the occurrence of tumours and prevent normal cells from becoming cancerous [ 40 , 51 , 56 , 57 , 58 , 59 ]. On the other hand, the process of autophagy may help tumour cell survival once carcinogenesis has occurred and, consequently, contributes to tumour progression.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

Catalani

Giovarelli

Zecchini

et al. 2021

Cancers

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Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.

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“…Macroautophagy (henceforth autophagy) is a cytoprotective mechanism critically involved in physiological and pathophysiological processes [1][2][3]. It is a constitutive activity for bulk degradation of damaged, aged or surplus organelles and aberrant protein aggregates, thus preserving cellular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…At the molecular level, autophagy is regulated by the coordinated action of autophagy-related (ATG) genes [1,4]. Autophagy is implicated in many human diseases and its therapeutic targeting has gained traction in recent years particularly for the treatment of cancer [1][2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Tight association of autophagy and cell cycle in leukemia cells

Gschwind

Marx

Just

et al. 2021

Preprint

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BackgroundAutophagy plays an essential role in maintaining cellular homeostasis and in the response to cellular stress. Autophagy is also involved in cell cycle progression, yet the relationship between these processes is not clearly defined.ResultsIn exploring this relationship, we observed that the inhibition of autophagy impaired the G2/M phase-arresting activity of etoposide but enhanced the G1 phase-arresting activity of palbociclib. We further investigated the connection of basal autophagy and cell cycle by utilizing the autophagosome tracer dye Cyto-ID in two ways. First, we established a double-labeling flow-cytometric procedure with Cyto-ID and the DNA probe DRAQ5, permitting the cell cycle phase-specific determination of autophagy in live cells. This approach demonstrated that different cell cycle phases were associated with different autophagy levels: G1 phase cells had the lowest one and G2/M phase cells had the highest one. Second, we developed a flow-cytometric cell sorting procedure based on Cyto-ID that separates cell populations into fractions with low, medium and high autophagy. Cell cycle analysis of Cyto-ID-sorted cells confirmed that the high autophagy fraction contained a much higher percentage of G2/M phase cells than the low autophagy fraction. Beyond that, Cyto-ID-based cell sorting proved also to be useful for assessing other autophagy-related processes: extracellular flux analysis revealed metabolic differences between the cell populations, with higher autophagy being associated with higher respiration, higher mitochondrial ATP production and higher glycolysis.ConclusionThis work sheds new light on the interrelation of autophagy and cell cycle by establishing a novel cell sorting technique based on Cyto-ID.

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Autophagy in major human diseases

Cited by 924 publications

References 798 publications

The Secrets of Alternative Autophagy

The Secrets of Alternative Autophagy

Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

Tight association of autophagy and cell cycle in leukemia cells

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