Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

Scheibye‐Knudsen, Morten; Ramamoorthy, Mahesh; Sýkora, Peter; Maynard, Scott; Lin, Ping Chang; Minor, Robin K.; Wilson, David M.; Cooper, Marcus P.; Spencer, Richard G.; Cabo, Rafael de; Croteau, Deborah L.; Bohr, Vilhelm A.

doi:10.1084/jem.20111721

Cited by 177 publications

(128 citation statements)

References 57 publications

(70 reference statements)

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“…Indeed, the induction of autophagy reduced mitochondrial loading and mitochondrial membrane potential in CSB cells, revealing that pharmacological modulation of this pathway is a promising approach. 109 Moreover, autophagy also has a role in stem cells maintenance, 110 suggesting that this pathway may also fight accelerated aging by maintaining the health of the stem cell population, avoiding loss of regenerative potential. 111 Accumulation of oxidatively generated damage has been implicated in several neurodegenerative diseases such as Parkinson's and Alzheimer's diseases.…”

Section: Parpmentioning

confidence: 99%

Autophagy and genomic integrity

et al. 2013

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DNA lesions, constantly produced by endogenous and exogenous sources, activate the DNA damage response (DDR), which involves detection, signaling and repair of the damage. Autophagy, a lysosome-dependent degradation pathway that is activated by stressful situations such as starvation and oxidative stress, regulates cell fate after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial genomic integrity. Here, we review important evidence regarding the role played by autophagy in preventing genomic instability and tumorigenesis, as well as in micronuclei degradation. Several pathways governing autophagy activation after DNA injury and the influence of autophagy upon the processing of genomic lesions are also discussed herein. In this line, the mechanisms by which several proteins participate in both DDR and autophagy, and the importance of this crosstalk in cancer and neurodegeneration will be presented in an integrated fashion. At last, we present a hypothetical model of the role played by autophagy in dictating cell fate after genotoxic stress.

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Section: Parpmentioning

confidence: 99%

Autophagy and genomic integrity

et al. 2013

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“…2,22,23,36,52,58,64,69 However, in vivo studies of rodent models did not show a consistent result for autophagy regulation by lithium, although behavioral abnormalities of all studies were improved. 46,49,54,66,72 This discrepancy is at least partly because of the lithium concentration. In tauopathy model mice, 4-month oral lithium treatment led to a 0.2 mM lithium plasma level and enhanced autophagy.…”

Section: Controversiesmentioning

confidence: 99%

“…metabolism in CSB m/m mice and CSB-deficient cells. 66 In CSBdeficient cells, damaged mitochondria and free radical production are increased and autophagy is downregulated. Lithium chloride or rapamycin 10 mM reverses the bioenergetics phenotype of CBS-deficient cells.…”

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confidence: 99%

Lithium and Autophagy

Motoi

Shimada

Ishiguro

et al. 2014

ACS Chem. Neurosci.

117

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Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms, including autophagy regulation, in various neuropsychiatric conditions. In neurodegenerative diseases, lithium enhances degradation of aggregate-prone proteins, including mutated huntingtin, phosphorylated tau, and α-synuclein, and causes damaged mitochondria to degrade, while in a mouse model of cerebral ischemia and Alzheimer's disease autophagy downregulation by lithium is observed. The signaling pathway of lithium as an autophagy enhancer might be associated with the mammalian target of rapamycin (mTOR)-independent pathway, which is involved in myoinositol-1,4,5-trisphosphate (IP 3 ) in Huntington's disease and Parkinson's disease. However, the mTOR-dependent pathway might be involved in inhibiting glycogen synthase kinase-3β (GSK3β) in other diseases. Lithium's autophagy-enhancing property may contribute to the therapeutic benefit of patients with neuropsychiatric disorders.

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“…Prior literature revealed mitochondrial deficits in A-T. 2 Since there are well-established links between DNA repair defects, neurodegeneration and mitochondrial dysfunction, 3,4 we focused our attention on mitochondria. In 2 other DNA repair-deficient syndromes, Cockayne Syndrome (CS), 4,5 and Xeroderma Pigmentosum group A (XPA), 3 we reported that persistent nuclear DNA damage created a signal to mitochondria, which we called nuclear to mitochondrial (NM) signaling.…”

mentioning

confidence: 99%

“…In 2 other DNA repair-deficient syndromes, Cockayne Syndrome (CS), 4,5 and Xeroderma Pigmentosum group A (XPA), 3 we reported that persistent nuclear DNA damage created a signal to mitochondria, which we called nuclear to mitochondrial (NM) signaling. 6 Nicotinamide adenine dinucleotide (NAD C ), an important metabolite in all human cells, was the signaling molecule.…”

mentioning

confidence: 99%