# Mitochondria-Associated MicroRNAs: Emerging Roles in the Pathogenesis of Parkinson’s Disease

**Authors:** Mariano Catanesi, Luana Di Leandro, Martina Colasante, Annamaria Cimini, Michele D’Angelo, Vanessa Castelli, Cosmin Marian Obreja, Rodolfo Ippoliti

PMC · DOI: 10.3390/biomedicines14020313 · Biomedicines · 2026-01-30

## TL;DR

This review explores how mitochondria-associated microRNAs may contribute to the development of Parkinson’s disease.

## Contribution

The paper highlights emerging evidence on the role of mitochondrial microRNAs in Parkinson’s disease pathogenesis.

## Key findings

- Mitochondrial dysfunction is a key feature of neurodegenerative diseases like Parkinson’s.
- Mito-MiRNAs regulate gene expression and metabolic activity within mitochondria.
- The functional roles of mito-MiRNAs in neurodegenerative disorders remain poorly understood.

## Abstract

Neurodegenerative diseases (NDs) are the most prevalent age-associated disorders, characterized by progressive neuronal loss and cognitive decline. Mitochondrial dysfunction is strictly associated with NDs and represent one of the hallmarks of these disorders, with neurological syndromes frequently representing the primary clinical manifestations of mitochondrial abnormalities. As central regulators of cellular bioenergetics, mitochondria play a pivotal role in both the physiological maintenance and pathogenesis of disease by different regulatory approaches. One of these, microRNAs (miRNAs), a class of small non-coding RNAs, are well-established regulators of gene expression across different biological pathways. These miRNAs were usually investigated within the cytoplasmic context, but recent discoveries have revealed the presence of these miRNAs in different parts of mitochondria, where they contribute to the regulation of gene expression and metabolic activity. These mitochondrial-localized miRNAs, termed mito-MiRNA, may originate from either nuclear or mitochondrial genomes and have been shown to modulate the translational machinery of the cells. Despite extensive research on cytoplasmic miRNAs, the functional roles of mito-MiRNA remain poorly understood, particularly in the context of neurodegenerative disorders. Based on these findings, this review aims to synthesize emerging evidence on the involvement of mito-MiRNA in in one of most prevalent neurodegenerative diseases—Parkinson’s disease (PD).

## Linked entities

- **Diseases:** Parkinson’s disease (MONDO:0005180)

## Full-text entities

- **Genes:** DROSHA (drosha ribonuclease III) [NCBI Gene 29102] {aka ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN}, MIR124-3 (microRNA 124-3) [NCBI Gene 406909] {aka MIRN124-3, MIRN124A3, mir-124-3}, ANKRD52 (ankyrin repeat domain 52) [NCBI Gene 283373] {aka ARSC, PP6-ARS-C}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], MIR27B (microRNA 27b) [NCBI Gene 407019] {aka MIR-27b, MIRN27B, miRNA27B}, Mir146a (microRNA 146a) [NCBI Gene 100314241] {aka rno-mir-146a}, MIR27A (microRNA 27a) [NCBI Gene 407018] {aka MIR27, MIRN27A, mir-27a}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, PNPT1 (polyribonucleotide nucleotidyltransferase 1) [NCBI Gene 87178] {aka COXPD13, DFNB70, OLD35, PNPASE, SCA25, old-35}, SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021] {aka ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3}, MFN1 (mitofusin 1) [NCBI Gene 55669] {aka hfzo1, hfzo2}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, TOMM20 (translocase of outer mitochondrial membrane 20) [NCBI Gene 9804] {aka MAS20, MOM19, TOM20}, Snca (synuclein alpha) [NCBI Gene 29219], LILRB1 (leukocyte immunoglobulin like receptor B1) [NCBI Gene 10859] {aka CD85J, ILT-2, ILT2, LIR-1, LIR1, MIR-7}, MIR193B (microRNA 193b) [NCBI Gene 574455] {aka MIRN193B, mir-193b}, PARK7 (Parkinsonism associated deglycase) [NCBI Gene 11315] {aka DJ-1, DJ1, GATD2, HEL-S-67p}, DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, Mir494 (microRNA 494) [NCBI Gene 723878] {aka Mirn494, mir-494, mmu-mir-494}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, Terf2 (telomeric repeat binding factor 2) [NCBI Gene 21750] {aka TRF2}, LRRK2 (leucine rich repeat kinase 2) [NCBI Gene 120892] {aka AURA17, DARDARIN, PARK8, RIPK7, ROCO2}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], Terf1 (telomeric repeat binding factor 1) [NCBI Gene 21749] {aka Pin2, Trbf1, Trf1}, COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}, PPP6C (protein phosphatase 6 catalytic subunit) [NCBI Gene 5537] {aka PP6, PP6C}, MIR150 (microRNA 150) [NCBI Gene 406942] {aka MIRN150, miRNA150, mir-150}, Mir132 (microRNA 132) [NCBI Gene 100314029] {aka rno-mir-132}, DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] {aka DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE}, XPO5 (exportin 5) [NCBI Gene 57510] {aka exp5}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, Vdac1 (voltage-dependent anion channel 1) [NCBI Gene 22333] {aka Vdac5, mVDAC1, mVDAC5}, Bcl2l11 (BCL2 like 11) [NCBI Gene 12125] {aka 1500006F24Rik, Bim, Bod, bcl2-L-11}, AGO1 (argonaute RISC component 1) [NCBI Gene 26523] {aka EIF2C, EIF2C1, GERP95, NEDLBAS, Q99, hAgo1}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, AMBRA1 (autophagy and beclin 1 regulator 1) [NCBI Gene 55626] {aka DCAF3, WDR94}, Tbpl2 (TATA box binding protein like 2) [NCBI Gene 227606] {aka Gm348, Trf3}, Park7 (Parkinson disease (autosomal recessive, early onset) 7) [NCBI Gene 57320] {aka DJ-1, Dj1}, SOCS1 (suppressor of cytokine signaling 1) [NCBI Gene 8651] {aka AISIMD, CIS1, CISH1, JAB, SOCS-1, SSI-1}, DNM1L (dynamin 1 like) [NCBI Gene 10059] {aka DLP1, DRP1, DVLP, DYMPLE, EMPF, EMPF1}, SAMM50 (SAMM50 sorting and assembly machinery component) [NCBI Gene 25813] {aka CGI-51, OMP85, SAM50, TOB55, TRG-3, YNL026W}, Mir155 (microRNA 155) [NCBI Gene 387173] {aka Mirn155, mir-155, mmu-mir-155}, MAOB (monoamine oxidase B) [NCBI Gene 4129], Nr4a2 (nuclear receptor subfamily 4, group A, member 2) [NCBI Gene 54278] {aka Nurr1, RNR1}, AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161] {aka CASC7, EIF2C2, LESKRES, LINC00980, PPD, Q10}, MFN2 (mitofusin 2) [NCBI Gene 9927] {aka CMT2A, CMT2A2, CMT2A2A, CMT2A2B, CPRP1, HMSN6A}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Bax (BCL2-associated X protein) [NCBI Gene 12028], APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, TrnI (tRNA-Ile) [NCBI Gene 17733], MIR214 (microRNA 214) [NCBI Gene 406996] {aka MIRN214, miRNA214, mir-214}
- **Diseases:** anosmia (MESH:D000857), dopaminergic (MESH:D009422), cognitive decline (MESH:D003072), motor disability (MESH:D009069), neurological and neuromuscular syndromes (MESH:D020879), dopaminergic neuron dysfunction (MESH:D009461), muscular rigidity (MESH:D009127), neuroblastoma (MESH:D009447), dementia (MESH:D003704), dysfunction (MESH:D006331), dopaminergic neuronal loss (MESH:D009410), mitochondrial fragmentation (MESH:D012892), dyskinesia (MESH:D004409), chronic pain (MESH:D059350), depression (MESH:D003866), toxicity (MESH:D064420), synucleinopathies (MESH:D000080874), hyposmia (MESH:D000086582), neuroinflammation (MESH:D000090862), essential tremor (MESH:D020329), cerebral atrophy (MESH:D001284), AD (MESH:D000544), reduced (MESH:D001523), diabetes mellitus (MESH:D003920), HD (MESH:D006816), resting (MESH:D014202), bradykinesia (MESH:D018476), PD (MESH:D010300), Mitochondrial dysfunction (MESH:D028361), injury to (MESH:D014947), NDs (MESH:D019636), inflammation (MESH:D007249), OS (MESH:D000079225), postural instability (MESH:D054972)
- **Chemicals:** glucose (MESH:D005947), heavy metals (MESH:D019216), calcium (MESH:D002118), ROS (MESH:D017382), dopamine (MESH:D004298), oligonucleotides (MESH:D009841), MPTP (MESH:D015632), lipid (MESH:D008055), ATP (MESH:D000255), rotenone (MESH:D012402), phosphatidylcholine (MESH:D010713), carbohydrates (MESH:D002241), carbidopa (MESH:D002230), oxygen (MESH:D010100), CTC (MESH:C072046), amantadine (MESH:D000547), BioRender (-), H2O2 (MESH:D006861), Levodopa (MESH:D007980)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** serine/threonine, L166P
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938016/full.md

## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938016/full.md

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Source: https://tomesphere.com/paper/PMC12938016