Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities

Abstract Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, and long-term stability of hematopoietic stem cells (HSCs). Recent research highlights the c...

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Main Authors: Yun Liao, Stacia Octaviani, Zhen Tian, Samuel R. Wang, Chunlan Huang, Jian Huang
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-025-04304-7
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author Yun Liao
Stacia Octaviani
Zhen Tian
Samuel R. Wang
Chunlan Huang
Jian Huang
author_facet Yun Liao
Stacia Octaviani
Zhen Tian
Samuel R. Wang
Chunlan Huang
Jian Huang
author_sort Yun Liao
collection DOAJ
description Abstract Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, and long-term stability of hematopoietic stem cells (HSCs). Recent research highlights the central importance of MQC in HSC biology, particularly the roles of mitophagy, mitochondrial biogenesis, fission, fusion and mitochondrial transfer in regulating HSC function. Mitophagy ensures the removal of damaged mitochondria, maintaining low levels of reactive oxygen species (ROS) in HSCs, thereby preventing premature aging and functional decline. Concurrently, mitochondrial biogenesis adjusts key metabolic regulators such as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring the metabolic needs of HSCs are met. Additionally, mitochondrial transfer, as an essential form of intercellular material exchange, facilitates the transfer of functional mitochondria from bone marrow stromal cells to HSCs, contributing to damage repair and metabolic support. Although existing studies have revealed the significance of MQC in maintaining HSC function, the precise molecular mechanisms and interactions among different regulatory pathways remain to be fully elucidated. Furthermore, the potential role of MQC dysfunction in hematopoietic disorders, including its involvement in disease progression and therapeutic resistance, is not yet fully understood. This review discusses the molecular mechanisms of MQC in HSCs, its functions under physiological and pathological conditions, and its potential therapeutic applications. By summarizing the current progress in this field, we aim to provide insights for further research and the development of innovative treatment strategies.
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spelling doaj-art-654bae0e2c2d4e9a933c88bc440248422025-08-20T02:17:46ZengBMCStem Cell Research & Therapy1757-65122025-04-0116111910.1186/s13287-025-04304-7Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunitiesYun Liao0Stacia Octaviani1Zhen Tian2Samuel R. Wang3Chunlan Huang4Jian Huang5Coriell Institute for Medical ResearchCoriell Institute for Medical ResearchCoriell Institute for Medical ResearchRutgers Cancer InstituteStem Cell Immunity and Regeneration Key Laboratory of LuzhouCoriell Institute for Medical ResearchAbstract Mitochondrial quality control (MQC) is a critical mechanism for maintaining mitochondrial function and cellular metabolic homeostasis, playing an essential role in the self-renewal, differentiation, and long-term stability of hematopoietic stem cells (HSCs). Recent research highlights the central importance of MQC in HSC biology, particularly the roles of mitophagy, mitochondrial biogenesis, fission, fusion and mitochondrial transfer in regulating HSC function. Mitophagy ensures the removal of damaged mitochondria, maintaining low levels of reactive oxygen species (ROS) in HSCs, thereby preventing premature aging and functional decline. Concurrently, mitochondrial biogenesis adjusts key metabolic regulators such as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) to meet environmental demands, ensuring the metabolic needs of HSCs are met. Additionally, mitochondrial transfer, as an essential form of intercellular material exchange, facilitates the transfer of functional mitochondria from bone marrow stromal cells to HSCs, contributing to damage repair and metabolic support. Although existing studies have revealed the significance of MQC in maintaining HSC function, the precise molecular mechanisms and interactions among different regulatory pathways remain to be fully elucidated. Furthermore, the potential role of MQC dysfunction in hematopoietic disorders, including its involvement in disease progression and therapeutic resistance, is not yet fully understood. This review discusses the molecular mechanisms of MQC in HSCs, its functions under physiological and pathological conditions, and its potential therapeutic applications. By summarizing the current progress in this field, we aim to provide insights for further research and the development of innovative treatment strategies.https://doi.org/10.1186/s13287-025-04304-7Mitochondrial quality controlHematopoietic stem cellMitochondrial metabolismMitophagyMitochondrial biogenesisMitochondrial dynamics
spellingShingle Yun Liao
Stacia Octaviani
Zhen Tian
Samuel R. Wang
Chunlan Huang
Jian Huang
Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
Stem Cell Research & Therapy
Mitochondrial quality control
Hematopoietic stem cell
Mitochondrial metabolism
Mitophagy
Mitochondrial biogenesis
Mitochondrial dynamics
title Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
title_full Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
title_fullStr Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
title_full_unstemmed Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
title_short Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities
title_sort mitochondrial quality control in hematopoietic stem cells mechanisms implications and therapeutic opportunities
topic Mitochondrial quality control
Hematopoietic stem cell
Mitochondrial metabolism
Mitophagy
Mitochondrial biogenesis
Mitochondrial dynamics
url https://doi.org/10.1186/s13287-025-04304-7
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AT samuelrwang mitochondrialqualitycontrolinhematopoieticstemcellsmechanismsimplicationsandtherapeuticopportunities
AT chunlanhuang mitochondrialqualitycontrolinhematopoieticstemcellsmechanismsimplicationsandtherapeuticopportunities
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