Table 1 List of modulator by mitophagy in stem cell or mitochondria modulator in stem cell

GP78

The increase of Gp78/AMFR (Gp78/autocrine motility factor receptor) expression and AMF (autocrine motility factor) internalization level in PTC (papillary thyroid carcinoma) is related to the expression of cancer stem cell markers

[1]

HIF-1 (hypoxia-inducible factor 1)

HIF1 mediates nuclear localization and TAZ (transcriptional co-activator with PDZ-binding motif) expression to induce the breast cancer stem cell phenotype

HIF1A reduces compression-induced apoptosis of nucleus pulposus stem cells by up-regulating autophagy

[2]

[3]

TBK1 (TANK binding kinase 1)

Zika virus disrupted the localization of phosphorylated TBK1 and mitosis in human neuroepithelial neural stem cells and radial glia

Retinoic acid aggravates ATG10 (Autophagy Related 10)-dependent autophagy damage in TBK1 mutant hiPSC s -derived motor neurons through SQSTM1/p62 accumulation

The replication of TBK1 stimulates autophagy in iPSC -derived retinal cells

Knockdown of TBK1 decreases Pca (prostate cancer) stem-like cells drug resistance in vivo and in vitro

[4]

[5]

[6]

[7]

OPTN (optineurin)

OPTN protects ESC mitochondrial homeostasis and pluripotency by eliminating damaged mitochondria through TBK1-activated OPTN binding of PINK1 -phosphorylated Ubiquitin

OPTN regulates bone fat balance and the fate of mesenchymal stem cells during aging by clearing FABP3 (fatty acid binding protein 3)

[8]

[9]

NIX(Nip-like protein X)

Silencing NIX impaired cancer stem cell maintenance, mitochondrial reactive oxygen species clearance

[10]

BNIP3 (Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3)

Hypoxia induces BNIP3 to stimulate the production of FASN (fatty acid synthase)-dependent free fatty acids and enhance the therapeutic potential of human mesenchymal stem cells derived from cord blood

Angelica polysaccharide down-regulates BNIP3 to regulate autophagy and apoptosis induced by hypoxia in rat neural stem cells

Promoting the expression of miR-210-3p can prevent NSC from hypoxic injury, which may reduce NSC cell apoptosis and AIF and BNIP3 expression levels

MiR-24-3p down-regulates BNIP3 in GSC to inhibit mitophagy

[11]

[12]

[13]

[14]

BMAL-1(Brain and muscle Arnt-like protein-1)

BMAL1 deficiency in hESC cardiomyocytes reduces BNIP3 protein levels and leads to impaired mitophagy

[15]

Pink1(PTEN-induced kinase 1)/Parkin

Intestinal stem cell (ISC)/EB-specific knockdown PINK1 or Parkin suppresses the age-related loss of tissue homeostasis

Parkin mediates mitophagy in insulin-deprived HCN (hippocampal neural stem) cells

Parkin-mediated mitophagy is necessary for the differentiation of MuSCs (Muscle stem cells) and plays a key role in skeletal muscle regeneration

In induced pluripotent stem cells, the endogenous level of Parkin is insufficient to initiate mitophagy after the loss of mitochondrial membrane potential

[16]

[17]

[18]

[19]

OPA1(optic Atrophy 1)/MFN (mitofusin)

Melatonin exerts a protective effect on Cr (VI)-induced mitophagy by restoring METTL3 (methyltransferase like 3)-mediated RNA mA modification and activating mitochondrial fusion proteins MFN2 (mitofusin2) and OPA1 (Optic Atrophy 1)

[20]

Miro (mitochondrial Rho GTPases)

Miro fixes mitochondria on the microtubule motor and is removed as an early step to clear dysfunctional mitochondria to prevent mitochondrial movement

Miro1 overexpression leads to increased stem cell repair

[21]

[22]

Fis1(mitochondrial fission factor)

AMPK (AMP-activated protein kinase)/FIS1 mediated mitophagy contributes to the self-renewal of human AML (acute myeloid leukemia) stem cells

FIS1 promotes the stemness of human lung cancer stem cells through mitophagy

[23]

[24]

Drp1 (Dynamin-related protein 1)

Drp1 is required for differentiation of embryonic stem cells

[25]

ULK1 (Unc-51-like kinase 1)

The phosphorylation of ULK1 by AMPK (AMP-activated protein kinase) is essential for the stemness regulation of ESC

The p53 activity in mouse embryonic stem cells is not required for the upregulation of ULK1-dependent autophagy

[26]

[27]

PCK2 (mitochondrial phosphoenolpyruvate carboxykinase)

PCK2 regulates the osteogenic differentiation of MSCs through autophagy-activated kinase 1 (ULK1)-dependent autophagy

[28]

PHB2 (Prohibitin 2)

PHB2 is a key mitochondrial regulator for homeostasis of embryonic stem cells

[29]

Apelin-13

Apelin-13 induces mitophagy and improves oxidative stressin bone marrow mesenchymal stem cells

[30]

MAPK (mitogen-activated protein kinase)

Bone marrow mesenchymal stem cells repair Cr (VI) damaged kidneys through mitophagy mediated by MAPK signaling pathway

[31]

KLF2 (Kruppel-like factor 2)

KLF2 regulates the differentiation of dental pulp stem cells by inducing mitophagy

[32]

METTL3 (methyltransferase like 3)

Melatonin protects mitophagy by restoring METTL3-mediated RNA mA modification

[20]

PEDF (Pigment epithelium-derived factor)

PEDF in placenta-derived mesenchymal stem cells (PD-MSCs) facilitate mitophagy and restore the loss of visual cycles in HO-injured rat retinas

[33]

Bhlhe40/Sirt1 (Sirtuin-1)

Bhlhe40/Sirt1 axis regulated mitophagy in neural stem cells

Sirt1selectively clears EGFR-TKI resistant CSCs by regulating mitochondrial oxidative phosphorylation in lung adenocarcinoma cells

[34]

[35]

SQSTM1/p62 (sequestosome 1)

SQSTM 1 has an effect on the early dependence of mitophagy, and its loss will lead to changes in the mitochondrial gene expression and function of iPSC-derived neurons

[36]

LRRc17 (leucine-rich repeat containing 17)

Knockout of LRRC 17 gene can rejuvenate aging bone marrow mesenchymal stem cells (BMSC)

[37]

Sirt3 (Sirtuin-3)

Sirt3-mediated mitophagy regulates AGEs (advanced glycation end products)-induced senescence of BMSCs

SIRT3 protects mitochondrial homeostasis by regulating mitophagy and promotes amniotic fluid stem cells to repair diabetic nephropathy

[38]

[39]

OGT (O-linked N-acetylglucosamine (O-GlcNAc) transferase)

OGT ensures mitochondrial quality through mitophagy, thereby regulating the maintenance and stress response of hematopoietic stem cells

[40]

NOD2 (domain-containing protein 2)

NOD2 mediates the protection of LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) intestinal stem cells against ROS cytotoxicity through mitophagy stimulation

[41]

TGF-β (Transforming growth factor β)

TGF-β1 enhances and accelerates the in vitro red blood cell formation of hematopoietic stem cells via stimulating mitophagy

TGF-β involves in the differentiation of chicken embryonic stem cells into male germ cells

[42]

[43]

HSPA1L (heat shock 70 kDa protein 1L)

Melatonin inhibits senescence-derived mitochondrial dysfunction in mesenchymal stem cells through the HSPA1L-mitophagy pathway

[44]

miRNA -322

MiRNA-322can self-renew and regulate mouse spermatogenic stem cells

[45]

p53

Down-regulation of p53 expression can reduce the accumulation of mitochondria in damaged cells and effectively resist stress-induced apoptosis and senescence of BMSCs

Mitophagy controls the activity of p53 to regulate liver cancer stem cells

[46]

[47]

FOXO3 (forkhead box O3)

FOXO3 is involved in the control of mitochondrial function of HSCs

[48]

2-hg (2-hydroxyglutaric acid)

Mitochondrial metabolism influences the fate of HSCs and determines their role in hematopoietic cells through 2-hg

[49]

Apaf-1 (apoptotic enzyme activation factor)

The lower expression of Apaf-1 in early differentiation of human embryonic neural stem cells against apoptosis

[50]

ISG15 (interferon-stimulated gene 15)

ISG15 is essential for optimized and effective OXPHOS, as it ensures the circulation of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts pancreatic cancer stem cells (PaCSCs) stemness

[51]

MF (Mangiferin)

MF promotes the phenotype of brown fat cells by inhibiting the mitophagy of mesenchymal stem cells

[52]

BAG5 (BCL2 associated athanogene 5)

Decrease of BAG5 leads to the instability of PINK1, thereby damaging mitophagy

[53]

mir-351-5p

The mitochondrial fission and accompanying mitophagy by miR-351-5p/Miro2 axis is critical in hippocampal neural progenitor cell death, and a potential therapeutic target in AD

[54]

Moringin

Moringin inhibits the expression of genes involved in mitophagy in human periodontal ligament stem cells

[55]

C89 (the small-molecule compound 89)

C89 induced autophagy involves in development and death of female germ stem cells through PI3K-AKT pathway

[56]

Memantine

Memantine enhances the mitochondrial degradation induced by iPSCs, and accelerated the clearance of damaged mitochondria through PINK1/parkin-mediated mitophagy

[57]

Pioglitazone

Pioglitazone has a significant inhibitory effect on autophagy of bone marrow mesenchymal stem cells, and it can protect mesenchymal stem cells from p-methylphenol-induced mitochondrial dysfunction by upregulation of PINK1

[58]

Printex 90

Printex 90 can inhibit the osteogenic differentiation and mitochondrial dysfunction of MSCs, and affect the regulation of mitochondrial biogenesis, kinetics and mitosis

[59]

Doxycycline (DOX)

The potent inhibition of EMT (epithelial-to-mesenchymal transition) and cancer stem-like characteristics in breast cancer cells by DOX treatment

[60]

PTBP1 (polypyrimidine binding protein 1)

Treatment with PTBP1 transformed the mitochondrial metabolism of CSCs in the colon to aerobic glycolysis, which may be related to the change in the characteristics of CSCs in the colon

[61]

Atad3a (ATPase family AAA-domain containing protein 3A)

Deletion of Atad3a induces hyperactivated mitophagy through Parkin/Pink1 pathway and impairs the homeostasis of HSCs and progenitor cells

[62]

DXR (doxorubicin)

The mitophagy level and expression of BNIP3L, a mitophagy regulator, were significantly higher in CSCs than in parental cells after DXR treatment

[63]

miR-1

Overexpression of a miR-1 could destroy mitochondria of cancer stem cells and induced mitophagy of cancer stem cells

[64]

Salinomycin

Salinomycin can induce mitophagy in some cells and may promote the differentiation of tumor stem cells by targeting the Wnt/β-catenin signaling pathway, thus eliminating tumor stem cells

[65]

DCA (dichloroacetate)

DCA can affect stemness-associated characteristics and mitochondrial function of pancreatic cancer cell lines

[66]

Nrf2 (nuclear factor erythroid 2-related factor 2)

Nrf2 is an essential molecule in the maintenance of CSCs’ stemness and self-renewal in response to different oxidative stresses such as chemotherapy-induced elevation of ROS

[67]