Organelle-Specific Initiation of Autophagy

Sica, Valentina; Galluzzi, Lorenzo; Pedro, José Manuel Bravo-San; Izzo, Valentina; Maiuri, Maria Chiara; Kroemer, Guido

doi:10.1016/j.molcel.2015.07.021

Cited by 182 publications

(125 citation statements)

References 145 publications

(245 reference statements)

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…9 Autophagy involves the formation of doublemembrane autophagosomes that engulf intracellular proteins and organelles and then fuse with lysosomes to form autolysosomes, where enveloped cargo is degraded. Although under certain specific conditions autophagy may contribute to cell death, 10 the liver basal autophagy seems to act as a cell survival function and is critical to maintain liver homeostasis. This notion is supported by the observations that genetic deletion of Atg5 or Atg7 in the mouse liver results in increased cell death and severe hepatomegaly and liver injury.…”

mentioning

confidence: 99%

Caspase Inhibition Prevents Tumor Necrosis Factor-α–Induced Apoptosis and Promotes Necrotic Cell Death in Mouse Hepatocytes in Vivo and in Vitro

McGill

Chao

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

How different cell death modes and cell survival pathways cross talk remains elusive. We determined the interrelation of apoptosis, necrosis, and autophagy in tumor necrosis factor (TNF)-a/actinomycin D (ActD) and lipopolysaccharide/D-galactosamine (GalN)-induced hepatotoxicity in vitro and in vivo. We found that TNF-a/ActD-induced apoptosis was completely blocked by a general caspase inhibitor ZVADfmk at 24 hours but hepatocytes still died by necrosis at 48 hours. Inhibition of caspases also protected mice against lipopolysaccharide/GalN-induced apoptosis and liver injury at the early time point, but this protection was diminished after prolonged treatment by switching apoptosis to necrosis. Inhibition of receptor-interacting protein kinase (RIP)1 by necrostatin 1 partially inhibited TNF-a/ZVAD-induced necrosis in primary hepatocytes. Pharmacologic inhibition of autophagy or genetic deletion of Atg5 in hepatocytes did not protect against TNF-a/ActD/ZVAD-induced necrosis. Moreover, pharmacologic inhibition of RIP1 or genetic deletion of RIP3 failed to protect and even exacerbated liver injury after mice were treated with lipopolysaccharide/GalN and a pan-caspase inhibitor. In conclusion, our results suggest that different cell death mode and cell survival pathways are closely integrated during TNF-ae induced liver injury when both caspases and NF-kB are blocked. Moreover, results from our study also raised concerns about the safety of currently ongoing clinical trials that use caspase inhibitors. (Am J Pathol 2016 http://dx

show abstract

mentioning

confidence: 99%

Caspase Inhibition Prevents Tumor Necrosis Factor-α–Induced Apoptosis and Promotes Necrotic Cell Death in Mouse Hepatocytes in Vivo and in Vitro

McGill

Chao

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Besides the molecular hallmark of receptor proteins, another criterion that has been applied to distinguish selective and nonselective autophagy pathways is the autophagy-triggering stimuli (Sica et al, 2015). It is commonly believed that starvation-triggered autophagy tends to be nonselective and can randomly engulf any cellular components to meet the heightened demand of cellular material recycling.…”

Section: Discussionmentioning

confidence: 99%

“…We chose to use the terms of ER autophagy and mitochondrial autophagy, not ER-phagy or mitophagy, to describe these processes, because the latter terms usually refer to selective autophagy pathways (Jin et al, 2013;Okamoto, 2014;Rogov et al, 2014;Sica et al, 2015;Khaminets et al, 2016), and it is not yet clear whether the starvation-induced organelle autophagy processes we observed here were selective or nonselective.…”

Section: Organelle Autophagy Is Induced By Nitrogen Starvation In S mentioning

confidence: 99%

Atg20- and Atg24-family proteins promote organelle autophagy in fission yeast

Zhao

Liu

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Autophagy cargos include not only soluble cytosolic materials but also bulky organelles, such as ER and mitochondria. In budding yeast, two proteins that contain the PX domain and the BAR domain, Atg20 and Atg24 (also known as Snx42 and Snx4, respectively) are required for organelle autophagy and contribute to general autophagy in a way that can be masked by compensatory mechanisms. It remains unclear why these proteins are important for organelle autophagy. Here, we show that in a distantly related fungal organism, the fission yeast Schizosaccharomyces pombe, autophagy of ER and mitochondria is induced by nitrogen starvation and is promoted by three Atg20-and Atg24-family proteins -Atg20, Atg24 and SPBC1711.11 (named here as Atg24b). These proteins localize at the pre-autophagosomal structure, or phagophore assembly site (PAS), during starvation. S. pombe Atg24 forms a homo-oligomer and acts redundantly with Atg20 and Atg24b, and the latter two proteins can form a hetero-oligomer. The organelle autophagy defect caused by the loss of these proteins is associated with a reduction of autophagosome size and a decrease in Atg8 accumulation at the PAS. These results provide new insights into the autophagic function of Atg20-and Atg24-family proteins.

show abstract

“…Triggered by lethal stimuli causing mitochondrial malfunction, PTEN-induced putative kinase 1 (PINK1) accumulates in the membrane of depolarized mitochondria, and initiates a mitophagic process by recruiting Parkin. Once recruited to the mitochondria, Parkin promotes autophagic degradation through the recruitment of LC3-containing autophagosomes to depolarized mitochondria (Narendra et al, 2010;Sica et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes

et al. 2016

View full text Add to dashboard Cite

-Trifloxystrobin is a strobilurin class fungicide, the mode of action of which is to block the mitochondrial electron transport chain and inhibit energy production in fungi. Although adverse effects have been reported by occupational or environmental exposure of fungicides, the pathophysiological mechanism in human cells remains poorly understood. In the present study, we investigated the impact of trifloxystrobin on exposed skin at the cellular organelle level using HaCaT, the human skin keratinocyte cell line. Cells were treated with trifloxystrobin for 48 hr and trifloxystrobin showed detrimental effects on mitochondria evidenced by altered mitochondrial membrane potential and morphology. To identify autophagic degradation of the damaged mitochondria, confocal imaging and Western blotting were performed. Trifloxystrobin induced autophagy-related proteins in HaCaT cells. The mitochondrial reactive oxygen species scavenger mitoTEMPO was applied to further explore the mechanism of trifloxystrobinmediated mitophagy in human skin cells. PINK1 and Parkin were overexpressed by trifloxystrobin, and mitoTEMPO alleviated the effects on mitophagy induction. Taken together, our findings indicated that mitochondrial damage and mitophagy may play a role in trifloxystrobin-induced toxicity in human keratinocytes and this could be suggested as a mechanism of cutaneous diseases developed by exposure.

show abstract

Organelle-Specific Initiation of Autophagy

Cited by 182 publications

References 145 publications

Caspase Inhibition Prevents Tumor Necrosis Factor-α–Induced Apoptosis and Promotes Necrotic Cell Death in Mouse Hepatocytes in Vivo and in Vitro

Caspase Inhibition Prevents Tumor Necrosis Factor-α–Induced Apoptosis and Promotes Necrotic Cell Death in Mouse Hepatocytes in Vivo and in Vitro

Atg20- and Atg24-family proteins promote organelle autophagy in fission yeast

Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes

Contact Info

Product

Resources

About