MAPK15-ULK1 signaling regulates mitophagy of airway epithelial cell in chronic obstructive pulmonary disease

Zhang, Ming; Fang, Lei; Zhou, Liang; Molino, Antonio; Valentino, Maria Rosaria; Yang, Shifeng; Zhang, Jie; Li, Yali; Roth, Michael

doi:10.1016/j.freeradbiomed.2021.07.004

Cited by 21 publications

(16 citation statements)

References 39 publications

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“…However, a drawback of these approaches is that several steps are required for proper staining and that cells die after staining. Similarly, it is possible to specifically measure ROS accumulated in mitochondria by using dyes that selectively targets mitochondria [12,[33][34][35]40,78,105].…”

Section: Methods For Detecting Oxidative Stressmentioning

confidence: 99%

“…Since mitochondrial respiration is a major source of cellular ROS, the strong impact that CSE has on mitochondrial activity significantly contributes to the observed oxidative damage [34]. Several reports have shown that CSE alters autophagy/mitophagy in bronchial epithelial cells by affecting the expression and the activity of several enzymes with a key role in these processes [12,31,105]. As an example, unc-51-like kinase 1 (ULK1) and mitogen-activated protein kinase 15 (MAPK15), the atypical member of the MAPK family, are involved in the signal transduction of conventional autophagy.…”

Section: Impact Of Cse On Autophagy Mitophagy and Mitochondrial Activitymentioning

confidence: 99%

“…Therefore, the inhibition of MAPK15-ULK1 signaling pathway might improve the function of airway epithelial cells and may represent a novel therapeutic strategy for COPD [29,105].…”

Section: Impact Of Cse On Autophagy Mitophagy and Mitochondrial Activitymentioning

confidence: 99%

“…Besides affecting apoptosis and promoting cell senescence, it has been reported that CSE promotes other inflammatory forms of cell death, such as the pyroptosis or other forms of caspase-dependent cell deaths [12,14,15,27,28,[30][31][32][33][34]68,69,72,73,105]. Pyroptosis is a type of pro-inflammatory cell death promoted by caspase-1 activation and characterized by cell lysis and interleukin IL-1β release.…”

Section: Impact Of Cse On Senescence and Cell Deathmentioning

confidence: 99%

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Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Cipollina

Bruno

Fasola

et al. 2022

IJMS

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Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

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Section: Methods For Detecting Oxidative Stressmentioning

confidence: 99%

Section: Impact Of Cse On Autophagy Mitophagy and Mitochondrial Activitymentioning

confidence: 99%

“…Therefore, the inhibition of MAPK15-ULK1 signaling pathway might improve the function of airway epithelial cells and may represent a novel therapeutic strategy for COPD [29,105].…”

Section: Impact Of Cse On Autophagy Mitophagy and Mitochondrial Activitymentioning

confidence: 99%

Section: Impact Of Cse On Senescence and Cell Deathmentioning

confidence: 99%

See 2 more Smart Citations

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Cipollina

Bruno

Fasola

et al. 2022

IJMS

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“…A role for the mitogen-activated protein kinase 15 (MAPK15; ERK8; ERK7) protein, an atypical member of the MAP kinase family, has been recently shown in different mechanisms used by cells to manage stressful stimuli. Starvation, ionizing radiations or chemical insult due to cigarette smoke are all examples of stimuli requiring MAPK15 for mounting a defensive cellular response (Lau & Xu, 2018;Zhang et al, 2021). Particularly, starvation induces a complex series of events aimed at preserving cell survival under conditions of limited availability of nutrients, with MAPK15 participating in many starvation-dependent cellular events among which Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-dependent induction of autophagy (Colecchia et al, 2012(Colecchia et al, , 2018.…”

Section: Introductionmentioning

confidence: 99%

MAPK15 protects from oxidative stress‐dependent cellular senescence by inducing the mitophagic process

et al. 2022

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Mitochondria are the major source of reactive oxygen species (ROS), whose aberrant production by dysfunctional mitochondria leads to oxidative stress, thus contributing to aging as well as neurodegenerative disorders and cancer. Cells efficiently eliminate damaged mitochondria through a selective type of autophagy, named mitophagy. Here, we demonstrate the involvement of the atypical MAP kinase family member MAPK15 in cellular senescence, by preserving mitochondrial quality, thanks to its ability to control mitophagy and, therefore, prevent oxidative stress. We indeed demonstrate that reduced MAPK15 expression strongly decreases mitochondrial respiration and ATP production, while increasing mitochondrial ROS levels. We show that MAPK15 controls the mitophagic process by stimulating ULK1‐dependent PRKN Ser108 phosphorylation and inducing the recruitment of damaged mitochondria to autophagosomal and lysosomal compartments, thus leading to a reduction of their mass, but also by participating in the reorganization of the mitochondrial network that usually anticipates their disposal. Consequently, MAPK15‐dependent mitophagy protects cells from accumulating nuclear DNA damage due to mitochondrial ROS and, consequently, from senescence deriving from this chronic DNA insult. Indeed, we ultimately demonstrate that MAPK15 protects primary human airway epithelial cells from senescence, establishing a new specific role for MAPK15 in controlling mitochondrial fitness by efficient disposal of old and damaged organelles and suggesting this kinase as a new potential therapeutic target in diverse age‐associated human diseases.

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Cyclophilin D Contributes to Airway Epithelial Mitochondrial Damage in Chronic Obstructive Pulmonary Disease

Zhang

Huang

et al. 2023

Lung

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MAPK15-ULK1 signaling regulates mitophagy of airway epithelial cell in chronic obstructive pulmonary disease

Cited by 21 publications

References 39 publications

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

MAPK15 protects from oxidative stress‐dependent cellular senescence by inducing the mitophagic process

Cyclophilin D Contributes to Airway Epithelial Mitochondrial Damage in Chronic Obstructive Pulmonary Disease

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