# Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde? **Authors:** María Beatriz Durán Alonso PMC · DOI: 10.3390/ijms27042053 · International Journal of Molecular Sciences · 2026-02-22 ## TL;DR This paper reviews how autophagy, a cellular cleanup process, can both protect and harm hearing cells under stress, suggesting it could be a target for treating hearing loss. ## Contribution The paper provides a comprehensive review of autophagy's dual role in cochlear damage and its potential as a therapeutic target. ## Key findings - Autophagy's role in cochlear damage is cell-type and context-dependent. - Modulating autophagy affects auditory cell survival and hearing impairment progression. - Reliable biomarkers and non-toxic modulators are needed for therapeutic applications. ## Abstract Autophagy plays a key role in the development and homeostasis of the cochlear organ. Alterations in the autophagic pathways have been associated with damage to auditory cell types and hearing impairment caused by an array of factors like age, ototoxicity, exposure to high levels of noise, or genetic mutations. Cochlear damage frequently entails mitochondrial dysfunction, impaired mitophagy and the accumulation of high concentrations of free radicals. This review summarizes the observations made to date on the autophagic function in response to cochlear damage and the results of either activating or inhibiting these processes. The data demonstrate that autophagic activity is cell context-dependent and varies according to the cochlear cell type, the toxic agent, its levels and the length and timing of its administration; other factors that influence the autophagic response may be external to the auditory system or related to epigenetic changes or the expression of genetic variants. Modulation of the autophagic status has an effect on auditory cell loss and the progression to hearing impairment and this approach has thus become a promising avenue towards the protection of the hearing function. Nonetheless, this is no easy task and it will require the identification of reliable biomarkers to evaluate the dynamics of autophagic activity as well as the development of specific autophagy modulators that do not exert toxicity. ## Linked entities - **Diseases:** hearing impairment (MONDO:0005365) ## Full-text entities - **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Slc7a14 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 14) [NCBI Gene 241919] {aka A930013N06}, Bak1 (BCL2-antagonist/killer 1) [NCBI Gene 12018] {aka Bak, N-BAK1, N-Bak}, Becn1 (beclin 1, autophagy related) [NCBI Gene 56208] {aka Atg6}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Mir183 (microRNA 183) [NCBI Gene 387178] {aka Mirn183, mir-183, mmu-mir-183}, Hcfc1 (host cell factor C1) [NCBI Gene 15161] {aka HCF, HCF1}, DAPK2 (death associated protein kinase 2) [NCBI Gene 23604] {aka DRP-1, DRP1}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Atg16l1 (autophagy related 16 like 1) [NCBI Gene 77040] {aka 1500009K01Rik, Apg16l, Atg16l, WDR30}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, Atg7 (autophagy related 7) [NCBI Gene 74244] {aka 1810013K23Rik, Agp7, Apg7l, Atg7l, Gm21553}, OSBPL2 (oxysterol binding protein like 2) [NCBI Gene 9885] {aka DFNA67, DIDA, DNFA67, ORP-2, ORP2}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Ddx11 (DEAD/H box helicase 11) [NCBI Gene 320209] {aka 4732462I11Rik, CHL1, CHLR1, KRG2, essa15a}, Pjvk (pejvakin) [NCBI Gene 381375] {aka Dfnb59, Gm1001}, Ythdf1 (YTH N6-methyladenosine RNA binding protein 1) [NCBI Gene 228994] {aka 2210410K23Rik, 8030473O16}, ATG7 (autophagy related 7) [NCBI Gene 10533] {aka APG7-LIKE, APG7L, GSA7, SCAR31}, Hspa8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 15481] {aka 2410008N15Rik, Hsc70, Hsc71, Hsc73, Hsp73, Hspa10}, Rab7 (RAB7, member RAS oncogene family) [NCBI Gene 19349] {aka Rab7a}, Vdac1 (voltage-dependent anion channel 1) [NCBI Gene 22333] {aka Vdac5, mVDAC1, mVDAC5}, GABARAP (GABA type A receptor-associated protein) [NCBI Gene 11337] {aka ATG8A, GABARAP-a, MM46}, Thap11 (THAP domain containing 11) [NCBI Gene 59016] {aka 2810036E22Rik, CTG-B43a, CTG-B45d, Ronin}, APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) [NCBI Gene 26060] {aka APPL, DIP13alpha, MODY14}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Mir34a (microRNA 34a) [NCBI Gene 723848] {aka Mirn34a, mir-34a, mmu-mir-34a}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 20846] {aka 2010005J02Rik}, RHEB (Ras homolog, mTORC1 binding) [NCBI Gene 6009] {aka RHEB2}, Map1lc3b (microtubule-associated protein 1 light chain 3 beta) [NCBI Gene 67443] {aka 1010001C15Rik, Atg8, LC3b, MAP1A/MAP1B, Map1lc3}, Atg4b (autophagy related 4B, cysteine peptidase) [NCBI Gene 66615] {aka 2510009N07Rik, Apg4b, Atg4bl, Autl1, MmAPG4B}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, Akt2 (Akt serine/threonine kinase 2) [NCBI Gene 11652] {aka 2410016A19Rik, PKB, PKBbeta}, Mapk10 (mitogen-activated protein kinase 10) [NCBI Gene 26414] {aka C230008H04Rik, JNK3, JNK3B1, JNK3B2, SAPK(beta), Serk2}, Map3k12 (mitogen-activated protein kinase kinase kinase 12) [NCBI Gene 26404] {aka DLK, MUK, Zpk}, GIPC3 (GIPC PDZ domain containing family member 3) [NCBI Gene 126326] {aka C19orf64, DFNB15, DFNB72, DFNB95}, CALCOCO2 (calcium binding and coiled-coil domain 2) [NCBI Gene 10241] {aka NDP52}, Keap1 (kelch-like ECH-associated protein 1) [NCBI Gene 50868] {aka INRF2, mKIAA0132}, Mir182 (microRNA 182) [NCBI Gene 387177] {aka Mirn182, mir-182, mmu-mir-182}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Aifm1 (apoptosis inducing factor, mitochondria associated 1) [NCBI Gene 83533] {aka Aif, Pdcd8}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Nqo1 (NAD(P)H dehydrogenase, quinone 1) [NCBI Gene 18104] {aka Dia4, Dtd, Nmo-1, Nmo1, Nmor1, Ox-1}, FOXG1 (forkhead box G1) [NCBI Gene 2290] {aka BF1, BF2, FHKL3, FKH2, FKHL1, FKHL2}, Tsc1 (TSC complex subunit 1) [NCBI Gene 64930], NCOA4 (nuclear receptor coactivator 4) [NCBI Gene 8031] {aka ARA70, ELE1, PTC3, RFG}, Tsc2 (TSC complex subunit 2) [NCBI Gene 22084] {aka Nafld, Tcs2}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Rptor (regulatory associated protein of MTOR, complex 1) [NCBI Gene 74370] {aka 4932417H02Rik, Rap, Raptor, mKIAA1303}, Ctsd (cathepsin D) [NCBI Gene 13033] {aka CD, CatD}, Crtc2 (CREB regulated transcription coactivator 2) [NCBI Gene 74343] {aka 4632407F12Rik, Torc2}, Lbh (limb-bud and heart) [NCBI Gene 77889] {aka 1810009F10Rik, 6720416L16Rik}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Sgk1 (serum/glucocorticoid regulated kinase 1) [NCBI Gene 20393] {aka Sgk}, Fgf1 (fibroblast growth factor 1) [NCBI Gene 14164] {aka Dffrx, Fam, Fgf-1, Fgf2b, Fgfa}, Txn1 (thioredoxin 1) [NCBI Gene 22166] {aka ADF, Trx1, Txn}, Nfatc4 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4) [NCBI Gene 73181] {aka 3110041H08Rik, Nfat3} - **Diseases:** Age (MESH:D019588), ferritinopathy (MESH:C548080), proteinopathies (MESH:D057165), ARHL (MESH:D010024), cytotoxicity (MESH:D064420), Ototoxicity (MESH:D006311), Fabry disease (MESH:D000795), diabetes (MESH:D003920), Cochlear damage (MESH:D015834), Non-syndromic deafness (MESH:D003638), auditory damage (MESH:D001304), Mitochondrial Dysfunction (MESH:D028361), death (MESH:D003643), Pompe disease (MESH:D006009), demyelination (MESH:D003711), AGs (MESH:C564013), Warsaw breakage syndrome (OMIM:613398), HC loss (MESH:D016388), inflammation (MESH:D007249), injury to (MESH:D014947), neurocognitive disease (MESH:D004194), hereditary non-syndromic deafness (MESH:D003123), non-syndromic SNHL (MESH:C580335), cell loss (MESH:D002292), NIHL (MESH:D006317), cognitive decline (MESH:D003072), HC damage (MESH:D020263), NPCD (MESH:D052556), necrosis (MESH:D009336), Sensorineural Hearing Loss (MESH:D006319), genetic neurological disorder (MESH:D030342), HL (MESH:D034381), ischemia (MESH:D007511), Gaucher disease (MESH:D005776), presbycusis (MESH:D011304), HSAN1E (MESH:D009477), HC degeneration (MESH:D009410), respiratory deficiencies (MESH:D012131), sleep deprivation (MESH:D012892) - **Chemicals:** chiisanoside (MESH:C507583), malondialdehyde (MESH:D008315), lipid peroxide (MESH:D008054), Rapamycin (MESH:D020123), phosphatidylserine (MESH:D010718), LPA (MESH:D010649), (-)-butaclamol (MESH:D002069), SB202190 (MESH:C090942), UA (MESH:D014527), Nobiletin (MESH:C008661), Sodium arsenite (MESH:C017947), tert-butyl hydroperoxide (MESH:D020122), 3-MA (MESH:C025946), polyADP-ribose (MESH:D011064), acetaminophen (MESH:D000082), Caffeine (MESH:D002110), cyclosporin A (MESH:D016572), thymoquinone (MESH:C003466), potassium (MESH:D011188), fasudil (MESH:C049347), Aminoglycoside (MESH:D000617), atorvastatin (MESH:D000069059), hydroxychloroquine (MESH:D006886), FK-506 (MESH:D016559), Tranylcypromine (MESH:D014191), phosphatidylethanolamine (MESH:C483858), temsirolimus (MESH:C401859), curcumin (MESH:D003474), N6-methyladenosine (MESH:C010223), AG (-), Cisplatin (MESH:D002945), platinum (MESH:D010984), H2O2 (MESH:D006861), D-galactose (MESH:D005690), Neomycin (MESH:D009355), C1 (MESH:C400149), chloroquine (MESH:D002738), ROS (MESH:D017382), 2,2',4,4'-tetrabromodiphenyl ether (MESH:C511295), Cholesterol (MESH:D002784), trehalose (MESH:D014199), kanamycin (MESH:D007612), lysophosphatidic acid (MESH:C032881), glucose (MESH:D005947), Cadmium (MESH:D002104), N-acetyl-L-cysteine (MESH:D000111), glutamate (MESH:D018698), mangiferin (MESH:C013592), GM (MESH:D005839), ascorbic acid (MESH:D001205), Spermidine (MESH:D013095), lead (MESH:D007854), NAD (MESH:D009243), Sevoflurane (MESH:D000077149), 2,3,4',5-tetrahydroxystilbene-2-O-beta-D-glucoside (MESH:C093026), coumarin (MESH:C030123), lipid (MESH:D008055), disaccharide (MESH:D004187), iron (MESH:D007501), imatinib mesylate (MESH:D000068877) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Danio rerio (leopard danio, species) [taxon 7955], HC [taxon 11103], Sus scrofa (pig, species) [taxon 9823], Gallus gallus (bantam, species) [taxon 9031], Cavia porcellus (domestic guinea pig, species) [taxon 10141] - **Mutations:** serine/threonine, m.1494C>T, rs510432, 1555A>G, 1494C>T - **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), HEI — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_1907), OC-1 — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_WL07), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), NIHL — Homo sapiens (Human), Transformed cell line (CVCL_M689), HEI-OC1 — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_D899), UB/OC-2 — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_D790) ## Full text _Full body text omitted from this summary view._ Fetch the complete 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