Related Experiment Video
Updated: Apr 8, 2026
10:17
Assessment of Cellular Bioenergetics in Mouse Hematopoietic Stem and Primitive Progenitor Cells using the Extracellular Flux Analyzer
Published on: September 24, 2021
3.3K
Non-necroptotic MLKL function damages mitochondria and promotes hematopoietic stem cell aging
Yuta Yamada1,2, Jinjing Yang2, Akiho Saiki-Tsuchiya2
1Division of Experimental Hematology, Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature Communications
|April 6, 2026
Summary
Hematopoietic stem cells (HSCs) decline with age due to stress responses. The RIPK3-MLKL pathway impairs HSC function and mitochondria, independent of cell death.
Area of Science:
- Cellular Biology
- Immunology
- Aging Research
Background:
- Hematopoietic stem cells (HSCs) lose function under stress and aging.
- Age-related HSC dysfunction is linked to mitochondrial impairment.
- The molecular link between HSC stress and aging is unclear.
Purpose of the Study:
- Investigate the molecular mechanisms connecting HSC stress response to age-related functional decline.
- Identify key pathways mediating HSC aging and mitochondrial dysfunction.
Main Methods:
- Analysis of HSC stress responses.
- Investigated the role of the RIPK3-MLKL axis in HSCs.
- Assessed MLKL accumulation and function in mitochondria.
- Studied MLKL's impact on HSC self-renewal and differentiation.
- Examined MLKL's role in age-related HSC changes.
Main Results:
- Multiple stress responses converge on the RIPK3-MLKL pathway in HSCs.
- Activated MLKL accumulates in HSC mitochondria, impairing self-renewal and lymphoid differentiation.
- MLKL mediates age-related mitochondrial damage and reduced glycolytic flux in HSCs.
- MLKL's function is independent of necroptosis (cell death).
Conclusions:
- The RIPK3-MLKL axis is a key mediator of HSC aging.
- MLKL plays a necroptosis-independent role in age-related mitochondrial damage and HSC functional decline.
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