# The regulation of mitochondrial ferritin on mitochondrial redox balance is essential to cell fate decision **Authors:** Yuanyuan Liu, Yan-Zhong Chang PMC · DOI: 10.1016/j.redox.2026.104124 · 2026-03-11 ## TL;DR Mitochondrial ferritin helps control iron levels in mitochondria, which affects cell survival and disease, offering new treatment possibilities. ## Contribution Highlights FtMt's unique role in mitochondrial redox balance and its implications for cell fate and disease. ## Key findings - FtMt isolates iron in mitochondria, reducing oxidative stress and maintaining redox balance. - FtMt influences cell fate decisions through regulation of mitochondrial integrity and redox homeostasis. - Dysregulation of FtMt is linked to neurodegenerative diseases, cardiovascular disorders, and aging-related conditions. ## Abstract Mitochondrial ferritin (FtMt), first identified by Levi et al., is an iron-storage protein with high homology with cytoplasmic ferritin. It is mainly expressed in metabolically active tissues and exhibits distinct physiological and biochemical properties compared cytoplasmic ferritin. Over the past few decades, significant attention has been drawn to the unique structural and functional characteristics of FtMt that differentiates it from conventional ferritin. Mitochondrial ferritin specifically located on the mitochondrial exhibits unique advantages in mitochondrial redox balance through isolating iron within mitochondria, reducing oxidative stress and maintaining mitochondrial homeostasis. Moreover, it modulates the labile iron pool within mitochondria, facilitating the biosynthesis of iron-sulfur clusters and supporting cellular respiration. This review comprehensively discusses the pivotal function of FtMt in regulating mitochondrial redox homeostasis and its impact on cell fate decisions, specifically, its influence on apoptosis, ferroptosis through alterations in mitochondrial integrity. We also summarize recent advances in understanding the association between FtMt dysregulation and various diseases, emphasizing its implications in neurodegenerative diseases, cardiovascular disorders and cerebrovascular pathologies. By critically evaluating emerging evidence, this article aims to provide translational insights into targeting FtMt and mitochondrial redox homeostasis as therapeutic strategies for mitigating these clinically significant diseases. •Mitochondrial ferritin (FtMt) can isolate free iron in mitochondria and participate in the regulation of mitochondrial redox balance.•FtMt participates in cellular energy generation and mitophagy processes.•FtMt participates in cell fate determination by regulating cellular redox balance.•FtMt plays an important protective role in various neurodegenerative, tumor, and aging-related diseases.•FtMt provides new therapeutic strategies for maintaining redox balance and disease intervention. Mitochondrial ferritin (FtMt) can isolate free iron in mitochondria and participate in the regulation of mitochondrial redox balance. FtMt participates in cellular energy generation and mitophagy processes. FtMt participates in cell fate determination by regulating cellular redox balance. FtMt plays an important protective role in various neurodegenerative, tumor, and aging-related diseases. FtMt provides new therapeutic strategies for maintaining redox balance and disease intervention. ## Linked entities - **Proteins:** FTMT (ferritin mitochondrial) ## Full-text entities - **Genes:** Ftmt (ferritin mitochondrial) [NCBI Gene 67634] {aka 4930447C24Rik, FerH, Fth3, MtF}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, ISCU (iron-sulfur cluster assembly enzyme) [NCBI Gene 23479] {aka 2310020H20Rik, HML, ISU2, NIFU, NIFUN, hnifU}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034] {aka ECYT4, HIF2A, HLF, MOP2, PASD2, bHLHe73}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, ME2 (malic enzyme 2) [NCBI Gene 4200] {aka ODS1}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, NCOA4 (nuclear receptor coactivator 4) [NCBI Gene 8031] {aka ARA70, ELE1, PTC3, RFG}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, FXN (frataxin) [NCBI Gene 2395] {aka CyaY, FA, FARR, FRDA, X25}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737] {aka AIEFL, IMD57, RIP, RIP-1, RIP1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, UOX (urate oxidase (pseudogene)) [NCBI Gene 391051] {aka UOXP, URICASE}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, SMG1 (SMG1 nonsense mediated mRNA decay associated PI3K related kinase) [NCBI Gene 23049] {aka 61E3.4, ATX, LIP}, SLC40A1 (solute carrier family 40 member 1) [NCBI Gene 30061] {aka FPN, FPN1, HFE4, IREG1, MST079, MSTP079}, BAK1 (BCL2 antagonist/killer 1) [NCBI Gene 578] {aka BAK, BAK-LIKE, BCL2L7, CDN1}, MAP1LC3B (microtubule associated protein 1 light chain 3 beta) [NCBI Gene 81631] {aka ATG8F, LC3B, MAP1A/1BLC3, MAP1LC3B-a}, CIRBP (cold inducible RNA binding protein) [NCBI Gene 1153] {aka CIRP}, NFS1 (NFS1 cysteine desulfurase) [NCBI Gene 9054] {aka COXPD52, HUSSY-08, IscS, NIFS}, CAT (catalase) [NCBI Gene 847], Ftmt (ferritin mitochondrial) [NCBI Gene 291470], FTH1 (ferritin heavy chain 1) [NCBI Gene 2495] {aka FHC, FTH, FTHL6, HFE5, NBIA9, PIG15}, FECH (ferrochelatase) [NCBI Gene 2235] {aka EPP, EPP1, FCE}, YY1 (YY1 transcription factor) [NCBI Gene 7528] {aka DELTA, GADEVS, INO80S, NF-E1, UCRBP, YIN-YANG-1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, RIPK3 (receptor interacting serine/threonine kinase 3) [NCBI Gene 11035] {aka RIP3}, GPX1 (glutathione peroxidase 1) [NCBI Gene 2876] {aka GPXD, GSHPX1}, TFRC (transferrin receptor) [NCBI Gene 7037] {aka CD71, IMD46, T9, TFR, TFR1, TR}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], FTMT (ferritin mitochondrial) [NCBI Gene 94033] {aka MTF}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, ABCB7 (ATP binding cassette subfamily B member 7) [NCBI Gene 22] {aka ABC7, ASAT, Atm1p, EST140535}, FTL (ferritin light chain) [NCBI Gene 2512] {aka FTL1, LFTD, NBIA3}, SLC11A2 (solute carrier family 11 member 2) [NCBI Gene 4891] {aka AHMIO1, DCT1, DMT1, NRAMP2}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, ACD (ACD shelterin complex subunit and telomerase recruitment factor) [NCBI Gene 65057] {aka DKCA6, DKCB7, PIP1, PTOP, TINT1, TPP1}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, OPA1 (OPA1 mitochondrial dynamin like GTPase) [NCBI Gene 4976] {aka BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, HAMP (hepcidin antimicrobial peptide) [NCBI Gene 57817] {aka HEPC, HFE2B, LEAP1, PLTR}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, GATA2 (GATA binding protein 2) [NCBI Gene 2624] {aka DCML, IMD21, MONOMAC, NFE1B}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, MLKL (mixed lineage kinase domain like pseudokinase) [NCBI Gene 197259] {aka hMLKL}, FOXA1 (forkhead box A1) [NCBI Gene 3169] {aka HNF3A, TCF3A} - **Diseases:** behavioral damage (MESH:D001523), neurobehavioral deficits (MESH:D019954), neurotoxic (MESH:D020258), PD (MESH:D010300), respiratory defects (MESH:D015619), cardiovascular diseases (MESH:D002318), cytotoxicity (MESH:D064420), neurodegenerative disease (MESH:D019636), ischemia (MESH:D007511), genetic degenerative disorder (MESH:D020271), I/R injury (MESH:D015427), ETC (MESH:D028361), fibrosarcoma (MESH:D005354), heart injury (MESH:D006335), Hemorrhage (MESH:D006470), ischemic stroke (MESH:D002544), sideroblastic anaemia (MESH:C536761), mtLIP (MESH:D005166), hemorrhagic stroke (MESH:D000083302), Stroke (MESH:D020521), /R (MESH:C580424), FRDA (MESH:D005621), T2DOP (MESH:D003924), iron overload (MESH:D019190), PCD (MESH:D003643), metastasis (MESH:D009362), CF (MESH:D006331), cerebral hemorrhage (MESH:D002543), Epilepsy (MESH:D004827), GMH (MESH:D054331), metabolic syndrome (MESH:D024821), vascular embolism (MESH:D004617), AD (MESH:D000544), necrosis (MESH:D009336), hypertension (MESH:D006973), hypoxic (MESH:D002534), osteoporosis (MESH:D010024), cardiotoxic (MESH:D066126), heart failure (MESH:D006333), seizures (MESH:D012640), inflammatory (MESH:D007249), MVFC (MESH:D060085), ovarian cancer (MESH:D010051), neuronal damage (MESH:D009410), Iron deficiency (MESH:D000090463), BBB damage (MESH:C536830), memory impairment (MESH:D008569), motor dysfunction (MESH:D000068079), systemic diseases (MESH:D034721), neuroblastoma (MESH:D009447), AMD (MESH:D008268), glioma (MESH:D005910), cerebrovascular disease (MESH:D002561), Friedrich's ataxia (MESH:D001259), OGD (MESH:C536050), Cancer (MESH:D009369), hereditary hemochromatosis (MESH:D006432), paralysis (MESH:D010243), brain tissue necrosis (MESH:D001927), glioblastoma (MESH:D005909) - **Chemicals:** 6-OHDA (MESH:D016627), KA (MESH:D007608), Fe-S (MESH:D007501), NADPH (MESH:D009249), DOX (MESH:D004317), lipid (MESH:D008055), pentose phosphate (MESH:D010428), 4Fe-4S (-), 3-Methyladenine (MESH:C025946), Calcium (MESH:D002118), superoxide (MESH:D013481), hypoxanthine (MESH:D019271), peroxide (MESH:D010545), DFO (MESH:D003676), FAC (MESH:C013531), Oxygen (MESH:D010100), MDA (MESH:D008315), TCA (MESH:D014233), FADH2 (MESH:C058805), xanthine (MESH:D019820), carbon (MESH:D002244), ATP (MESH:D000255), metal (MESH:D008670), flavin adenine dinucleotide (MESH:D005182), DFP (MESH:D000077543), Sulfur (MESH:D013455), acetyl-coA (MESH:D000105), 59Fe (MESH:C000615388), FeCl2 (MESH:C029451), delta-aminolevulinic acid (MESH:D000622), Heme (MESH:D006418), selenium (MESH:D012643), tyrosine (MESH:D014443), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), tBHP (MESH:D020122), glucose (MESH:D005947), Roflumilast (MESH:C424423), glycine (MESH:D005998), antimycin A (MESH:D000968), isoproterenol (MESH:D007545), H2O (MESH:D014867), PUFA (MESH:D005231), CCCP (MESH:D002258), ROS (MESH:D017382), NADH (MESH:D009243), hydroxyl radicals (MESH:D017665), lipid hydroperoxides (MESH:D008054), 55Fe (MESH:C000615387), Carbonyl Cyanide (MESH:C100076), protoporphyrin IX (MESH:C028025), GSH (MESH:D005978), cysteine (MESH:D003545), Erastin (MESH:C477224), H2O2 (MESH:D006861), glutamate (MESH:D018698), coenzyme Q (MESH:D014451) - **Species:** Homo sapiens (human, species) [taxon 9606], Pan troglodytes (chimpanzee, species) [taxon 9598], Adeno-associated virus (species) [taxon 272636], Drosophila melanogaster (fruit fly, species) [taxon 7227], Mus musculus (house mouse, species) [taxon 10090], Cercopithecidae (monkey, family) [taxon 9527], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Rattus norvegicus (brown rat, species) [taxon 10116] - **Mutations:** serine residue at position 144, tyrosine residue at position 40, tyrosine residue at position 34 - **Cell lines:** K256 — Homo sapiens (Human), Medulloblastoma, Cancer cell line (CVCL_DG09), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HT22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321), IMR-32 — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0346), ARPE-19 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145), H1299 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0060), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019) ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13010531/full.md --- Source: https://tomesphere.com/paper/PMC13010531