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Open AccessArticle

Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell

by 1,2,*, 2, 2 and 1
1
Division of Cardiovascular Diseases, Center for Biomedical Sciences, National Institute of Health, Cheongju-si 28159, Chungbuk, Korea
2
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5869; https://doi.org/10.3390/ijms21165869
Received: 9 July 2020 / Revised: 3 August 2020 / Accepted: 13 August 2020 / Published: 15 August 2020
(This article belongs to the Special Issue Physiology of Platelets in Humans and Animals)
Increased platelet activation and apoptosis are characteristic of diabetic (DM) platelets, where a Parkin-dependent mitophagy serves a major endogenous protective role. We now demonstrate that Parkin is highly expressed in both healthy platelets and diabetic platelets, compared to other mitochondria-enriched tissues such as the heart, muscle, brain, and liver. Abundance of Parkin in a small, short-lived anucleate cell suggest significance in various key processes. Through proteomics we identified 127 Parkin-interacting proteins in DM platelets and compared them to healthy controls. We assessed the 11 highest covered proteins by individual IPs and confirmed seven proteins that interacted with Parkin; VCP/p97, LAMP1, HADHA, FREMT3, PDIA, ILK, and 14-3-3. Upon further STRING analysis using GO and KEGG, interactions were divided into two broad groups: targeting platelet activation through (1) actions on mitochondria and (2) actions on integrin signaling. Parkin plays an important role in mitochondrial protection through mitophagy (VCP/p97), recruiting phagophores, and targeting lysosomes (with LAMP1). Mitochondrial β-oxidation may also be regulated by the Parkin/HADHA interaction. Parkin may regulate platelet aggregation and activation through integrin signaling through interactions with proteins like FREMT3, PDIA, ILK, and 14-3-3. Thus, platelet Parkin may regulate the protection (mitophagy) and stress response (platelet activation) in DM platelets. This study identified new potential therapeutic targets for platelet mitochondrial dysfunction and hyperactivation in diabetes mellitus. View Full-Text
Keywords: platelet; diabetes; Parkin platelet; diabetes; Parkin
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MDPI and ACS Style

Lee, S.H.; Du, J.; Hwa, J.; Kim, W.-H. Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell. Int. J. Mol. Sci. 2020, 21, 5869. https://doi.org/10.3390/ijms21165869

AMA Style

Lee SH, Du J, Hwa J, Kim W-H. Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell. International Journal of Molecular Sciences. 2020; 21(16):5869. https://doi.org/10.3390/ijms21165869

Chicago/Turabian Style

Lee, Seung H.; Du, Jing; Hwa, John; Kim, Won-Ho. 2020. "Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell" Int. J. Mol. Sci. 21, no. 16: 5869. https://doi.org/10.3390/ijms21165869

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