Programmed anuclear cell death delimits platelet life span

Kylie D Mason, Marina Carpinelli, Jamie I Fletcher, Janelle Elyse Collinge, Adrienne A Hilton, Sarah L Ellis, Priscilla Kelly, Paul G Ekert, Donald Metcalf, Andrew W Roberts, David CS Huang, Benjamin T Kile

Research output: Contribution to journalArticleResearchpeer-review

853 Citations (Scopus)


Platelets are anuclear cytoplasmic fragments essential for blood clotting and wound healing. Despite much speculation, the factors determining their life span in the circulation are unknown. We show here that an intrinsic program for apoptosis controls platelet survival and dictates their life span. Pro-survival Bcl-xL constrains the pro-apoptotic activity of Bak to maintain platelet survival, but as Bcl-xL degrades, aged platelets are primed for cell death. Genetic ablation or pharmacological inactivation of Bcl-xL reduces platelet half-life and causes thrombocytopenia in a dose-dependent manner. Deletion of Bak corrects these defects, and platelets from Bak-deficient mice live longer than normal. Thus, platelets are, by default, genetically programmed to die by apoptosis. The antagonistic balance between Bcl-xL and Bak constitutes a molecular clock that determines platelet life span: this represents an important paradigm for cellular homeostasis, and has profound implications for the diagnosis and treatment of disorders that affect platelet number and function.
Original languageEnglish
Pages (from-to)1173 - 1186
Number of pages14
Issue number6
Publication statusPublished - 2007
Externally publishedYes

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