Inducing mitophagy in diabetic platelets protects against severe oxidative stress
Blood Platelets
0301 basic medicine
Medicine (General)
MAP Kinase Signaling System
Mitophagy
Apoptosis
QH426-470
3. Good health
Oxidative Stress
03 medical and health sciences
mitophagy
R5-920
diabetes mellitus
platelets
Genetics
Diabetes Mellitus
oxidative stress
Humans
Phosphorylation
Tumor Suppressor Protein p53
Protein Processing, Post-Translational
Research Articles
DOI:
10.15252/emmm.201506046
Publication Date:
2016-05-25T00:45:39Z
AUTHORS (16)
ABSTRACT
Diabetes mellitus (DM) is a growing international concern. Considerable mortality and morbidity associated with diabetes mellitus arise predominantly from thrombotic cardiovascular events. Oxidative stress-mediated mitochondrial damage contributes significantly to enhanced thrombosis in DM A basal autophagy process has recently been described as playing an important role in normal platelet activation. We now report a substantial mitophagy induction (above basal autophagy levels) in diabetic platelets, suggesting alternative roles for autophagy in platelet pathology. Using a combination of molecular, biochemical, and imaging studies on human DM platelets, we report that platelet mitophagy induction serves as a platelet protective mechanism that responds to oxidative stress through JNK activation. By removing damaged mitochondria (mitophagy), phosphorylated p53 is reduced, preventing progression to apoptosis, and preserving platelet function. The absence of mitophagy in DM platelets results in failure to protect against oxidative stress, leading to increased thrombosis. Surprisingly, this removal of damaged mitochondria does not require contributions from transcription, as platelets lack a nucleus. The considerable energy and resources expended in "prepackaging" the complex mitophagy machinery in a short-lived normal platelet support a critical role, in anticipation of exposure to oxidative stress.
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