AMPK-independent induction of autophagy by cytosolic Ca2+ increase

Grotemeier, Antje; Alers, Sebastian; Pfisterer, Simon G.; Paasch, Florian; Daubrawa, Merle; Dieterle, Alexandra; Viollet, Benoı̂t; Wesselborg, Sebastian; Proikas‐Cezanne, Tassula; Stork, Björn

doi:10.1016/j.cellsig.2010.01.015

Cited by 143 publications

(145 citation statements)

References 29 publications

Supporting

Mentioning

135

Contrasting

Order By: Relevance

“…An increase in Ca 2C levels in Pompe cells could lead to the increased autophagy, but this relationship is a subject of controversy. A number of studies suggested that a rise in cytosolic Ca 2C is a powerful inducer of autophagy, [68][69][70][71] although other reports do not support this finding. 72,73 In our study, the normalization of Ca 2C levels by verapamil did not have any appreciable effect on autophagy.…”

Section: Discussioncontrasting

confidence: 43%

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

et al. 2015

View full text Add to dashboard Cite

Section: Discussioncontrasting

confidence: 43%

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

et al. 2015

View full text Add to dashboard Cite

“…Previous studies have reported induction of noncanonical autophagy in an MTOR-independent fashion by various stimuli. [62][63][64][65][66] Notably, studies by Cheong et al have also shown that ulk1 and ulk2 double-null MEFs induce autophagy under glucose deprivation conditions through accumulation of ammonia from amino acid catabolism. 67 However, to our knowledge, there has been no report documenting basal as well as hypoxiainduced autophagy being regulated independently of the MTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling

et al. 2016

View full text Add to dashboard Cite

Nucleus pulposus (NP) cells reside in the avascular and hypoxic microenvironment of intervertebral discs. Importantly, many activities related to survival and function of NP cells are controlled by the HIF-family of transcription factors. We hypothesize that NP cells adapt to their hypoxic niche through modulation of macroautophagy/autophagy. In various cell types, hypoxia induces autophagy in a HIF1A-dependent fashion; however, little is known about hypoxic regulation of autophagy in NP cells. Hypoxia increases the number of autophagosomes as seen by TEM analysis and LC3-positive puncta in NP cells. Hypoxic induction of autophagy was also demonstrated by a significantly higher number of autophagosomes and smaller change in autolysosomes in NP cells expressing tandem-mCherry-EGFP-LC3B. Increased LC3-II levels were not accompanied by a concomitant increase in BECN1 or the ATG12-ATG5 complex. In addition, ULK1 phosphorylation at Ser757 and Ser777 responsive to MTOR and AMPK, respectively, was not affected in hypoxia. Interestingly, when MTOR activity was inhibited by rapamycin or Torin1, LC3-II levels did not change, suggesting a novel MTOR-independent regulation. Noteworthy, while silencing of HIF1A affected hypoxic induction of BNIP3, it did not affect LC3-II levels, indicating hypoxia-induced autophagy is HIF1-independent. Importantly, there was no change in the number of LC3-positive autophagosomes in NP-specific Hif1a null mice. Finally, inhibition of autophagic flux did not affect the glycolytic metabolism of NP cells, suggesting a possible nonmetabolic role of autophagy. Taken together, our study for the first time shows that NP cells regulate autophagy in a noncanonical fashion independent of MTOR and HIF1A signaling.

show abstract

“…Ca 2+ partici- pates in formation of autophagosome as an important regulatory factor. It modulates localization of atg18 to autophagosomal membranes [15] . Removal of intracellular calcium can inhibit autophagy.…”

Section: Observation Of Ultrastructural Morphology Of Autophagosomementioning

confidence: 99%

“…Intracellular free calcium concentration ([Ca 2+ ] i ) and mitochondrial membrane potential (MMP) are important indicators to reflect cell injury. It is reported that autophagy can be induced by increased [Ca 2+ ] i and decreased MMP [15,16] . Beclin-1, an autophagy related gene, is an essential indicator of autophagy.…”

Section: Introductionmentioning

confidence: 99%

β-Asarone protects PC12 cells against OGD/R-induced injury via attenuating Beclin-1-dependent autophagy

Fang

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To explore the effects of β-asarone from Acorus Tatarinowii Schott on autophagy in an ischemic stroke model of PC12 cells. Methods: The ischemic stroke model of PC12 cells was made by OGD/R (2 h oxygen-glucose deprivation followed by 24 h reperfusion). Drug administration was started 1 h before OGD and last for 3 h. Then the cells were incubated in the drug-free and full culture medium under normoxic conditions for 24 h. After the treatments, Beclin-1, intracellular free calcium concentration ([Ca 2+ ] i ) and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. Cell viability was measured using MTT assay. Cell morphology was studied under inverted phase contrast microscope, and autophagosomes were observed under transmission electron microscope.

show abstract

AMPK-independent induction of autophagy by cytosolic Ca2+ increase

Cited by 143 publications

References 29 publications

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling

β-Asarone protects PC12 cells against OGD/R-induced injury via attenuating Beclin-1-dependent autophagy

Contact Info

Product

Resources

About