Autophagy is important for maintaining cellular homeostasis, and thus its deficiency is implicated in a broad spectrum of human diseases. Its role in platelet function has only recently been examined. Our biochemical and imaging studies demonstrate that the core autophagy machinery exists in platelets, and that autophagy is constitutively active in resting platelets. Moreover, autophagy is induced upon platelet activation, as indicated by agonist-induced loss of the autophagy marker LC3II. Additional experiments, using inhibitors of platelet activation, proteases, and lysosomal acidification, as well as platelets from knockout mouse strains, show that agonist-induced LC3II loss is a consequence of platelet signaling cascades and requires proteases, acidic compartments, and membrane fusion. To assess the physiological role of platelet autophagy, we generated a mouse strain with a megakaryocyte- and platelet-specific deletion of Atg7, an enzyme required for LC3II production. Ex vivo analysis of platelets from these mice shows modest defects in aggregation and granule cargo packaging. Although these mice have normal platelet numbers and size distributions, they exhibit a robust bleeding diathesis in the tail-bleeding assay and a prolonged occlusion time in the FeCl3-induced carotid injury model. Our results demonstrate that autophagy occurs in platelets and is important for hemostasis and thrombosis.

Document Type


Publication Date


Notes/Citation Information

Published in Blood, v. 126, no. 10, p. 1224-1233.

This research was originally published in Blood. Madhu M. Ouseph, Yunjie Huang, Meenakshi Banerjee, Smita Joshi, Laura MacDonald, Yu Zhong, Huijuan Liu, Xianting Li, Binggang Xiang, Guoying Zhang, Masaaki Komatsu, Zhenyu Yue, Zhenyu Li, Brian Storrie, Sidney W. Whiteheart and Qing Jun Wang. Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood. 2015;1224-1233. © 2015 by The American Society of Hematology

The copyright holder has granted the permission for posting the article here.

An erratum to this article is available as the additional file listed below and online at https://doi.org/10.1182/blood-2015-09-668111.

Digital Object Identifier (DOI)


Funding Information

This work was supported by National Institutes of Health Grants P20GM103486 (National Institute of General Medical Sciences; to Q.J.W.), HL56652 and HL091893 (National Heart, Lung, and Blood Institute; to S.W.W.), R01NS060123 (National Institute of Neurological Disorders; to Z.Y.), and R01HL119393 (National Heart, Lung, and Blood Institute; to B.S.); the Ellison Medical Foundation (Q.J.W.); University of Kentucky Research Support Grant and start-up fund (Q.J.W.); and American Heart Association Predoctoral Fellowship (Y.H.).

Related Content

The online version of this article contains a data supplement.

blood-2014-09-598722-1.pdf (1476 kB)
Data supplement: Document 1. Supplemental methods, figures, and table

2072.1.full.pdf (425 kB)