Nitric Oxide Induction of Parkin Translocation in PTEN-induced Putative Kinase 1 (PINK1) Deficiency

Han, Junghee; Kang, Minji; Kim, Kyung‐Hee; Han, Pyung-Lim; Ha, Ji‐Young; Son, Jin H.

doi:10.1074/jbc.m114.624767

Cited by 32 publications

(27 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disruption of either leads to the failure of selective degradation of impaired mitochondria 51, 52. Loss of the mitochondrial membrane potential triggers PINK1 accumulation on the surface of mitochondria and phosphorylates mitochondrial outer membrane proteins 49, 53.…”

Section: Discussionmentioning

confidence: 99%

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

Wang

Zhao

Feng

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Mitophagy eliminates dysfunctional mitochondria and thus plays a cardinal role in diabetic cardiomyopathy (DCM). We observed the favourable effects of melatonin on cardiomyocyte mitophagy in mice with DCM and elucidated their underlying mechanisms. Electron microscopy and flow cytometric analysis revealed that melatonin reduced the number of impaired mitochondria in the diabetic heart. Other than decreasing mitochondrial biogenesis, melatonin increased the clearance of dysfunctional mitochondria in mice with DCM. Melatonin increased LC3 II expression as well as the colocalization of mitochondria and lysosomes in HG‐treated cardiomyocytes and the number of typical autophagosomes engulfing mitochondria in the DCM heart. These results indicated that melatonin promoted mitophagy. When probing the mechanism, increased Parkin translocation to the mitochondria may be responsible for the up‐regulated mitophagy exerted by melatonin. Parkin knockout counteracted the beneficial effects of melatonin on the cardiac mitochondrial morphology and bioenergetic disorders, thus abolishing the substantial effects of melatonin on cardiac remodelling with DCM. Furthermore, melatonin inhibited Mammalian sterile 20‐like kinase 1 (Mst1) phosphorylation, thus enhancing Parkin‐mediated mitophagy, which contributed to mitochondrial quality control. In summary, this study confirms that melatonin rescues the impaired mitophagy activity of DCM. The underlying mechanism may be attributed to activation of Parkin translocation via inhibition of Mst1.

show abstract

Section: Discussionmentioning

confidence: 99%

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

Wang

Zhao

Feng

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…[47][48][49][50][51] The initial report showing that selective mitophagy occurs in PINK1-deficient neuroblastoma cells 51 was followed by studies showing that Parkin may be recruited through PINK1-independent mechanisms both in vitro and in vivo. 52,53 Pathways independent of both PINK1 and Parkin have also emerged, often involving mitophagy stimuli that cause lesser degrees of or no mitochondrial depolarization. 6,16 Several mitophagy adaptor proteins (NIX, BNIP3, and FUNDC1) are upregulated or post-translationally modified during developmental or hypoxia-induced mitophagy to directly interact with LC3 via a LIR to recruit autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy

Kagan¹,

Jiang²,

Huang³

et al. 2016

Cell Death Differ

161

133

View full text Add to dashboard Cite

Mitophagy is critical for cell homeostasis. Externalization of the inner mitochondrial membrane phospholipid, cardiolipin (CL), to the surface of the outer mitochondrial membrane (OMM) was identified as a mitophageal signal recognized by the microtubuleassociated protein 1 light chain 3. However, the CL-translocating machinery remains unknown. Here we demonstrate that a hexameric intermembrane space protein, NDPK-D (or NM23-H4), binds CL and facilitates its redistribution to the OMM. We found that mitophagy induced by a protonophoric uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), caused externalization of CL to the surface of mitochondria in murine lung epithelial MLE-12 cells and human cervical adenocarcinoma HeLa cells. RNAi knockdown of endogenous NDPK-D decreased CCCP-induced CL externalization and mitochondrial degradation. A R90D NDPK-D mutant that does not bind CL was inactive in promoting mitophagy. Similarly, rotenone and 6-hydroxydopamine triggered mitophagy in SH-SY5Y cells was also suppressed by knocking down of NDPK-D. In situ proximity ligation assay (PLA) showed that mitophagy-inducing CL-transfer activity of NDPK-D is closely associated with the dynamin-like GTPase OPA1, implicating fission-fusion dynamics in mitophagy regulation.

show abstract

“…This process is not dependent on Parkin, suggesting a previously unrecognized ability of PINK1 to directly induce mitophagy [19]. Similarly, Parkin can translocate to damaged mitochondria to induce mitophagy in PINK1 deficient cardiomyocytes or neuronal cells, suggesting the existence of as yet unidentified PINK1-independent mechanisms that can activate Parkin and induce mitophagy[107, 108]. …”

Section: Autophagy Mitophagy and Their Regulatory Pathwaysmentioning

confidence: 99%

Mitochondrial quality control in the diabetic heart

Liang

Kobayashi

2016

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Diabetes is a well known risk factor for heart failure. Diabetic heart damage is closely related to mitochondrial dysfunction and increased ROS generation. However, clinical trials have shown no effects of antioxidant therapies on heart failure in diabetic patients, suggesting that simply antagonizing existing ROS by antioxidants is not sufficient to reduce diabetic cardiac injury. A potentially more effective treatment strategy may be to enhance the overall capacity of mitochondrial quality control to maintain a pool of healthy mitochondria that are needed for supporting cardiac contractile function in diabetic patients. Mitochondrial quality is controlled by a number of coordinated mechanisms including mitochondrial fission and fusion, mitophagy and biogenesis. The mitochondrial damage consistently observed in the diabetic hearts indicates a failure of the mitochondrial quality control mechanisms. Recent studies have demonstrated a crucial role for each of these mechanisms in cardiac homeostasis and have begun to interrogate the relative contribution of insufficient mitochondrial quality control to diabetic cardiac injury. In this review, we will present currently available literature that links diabetic heart disease to the dysregulation of major mitochondrial quality control mechanisms. We will discuss the functional roles of these mechanisms in the pathogenesis of diabetic heart disease and their potentials for targeted therapeutical manipulation.

show abstract

Nitric Oxide Induction of Parkin Translocation in PTEN-induced Putative Kinase 1 (PINK1) Deficiency

Cited by 32 publications

References 55 publications

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition

NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy

Mitochondrial quality control in the diabetic heart

Contact Info

Product

Resources

About