Evidence mapPaperPMID 41454179Full record

ReviewNeurotoxicity research2025

The Role of Mitochondrial Quality Control in Manganese-induced Neurotoxicity.

Alexey A Tinkov, Hyunjin Kim, Anatoly V Skalny, Jung-Su Chang, Abel Santamaria, Rongzhu Lu, Ji-Chang Zhou, Aaron B Bowman, Eun-Sook Lee, Yousef Tizabi and 1 more

Abstract readReview
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In one paragraph

Review in Neurotoxicity research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Alexey A TinkovInstitute of Bioelementology, Orenburg State University, 460018, Orenburg, Russia. tinkov.a.a@gmail.com.
Hyunjin KimSchool of Health Sciences, Purdue University, IN, 47907-2051, West Lafayette, USA.
Anatoly V SkalnyInstitute of Bioelementology, Orenburg State University, 460018, Orenburg, Russia.
Jung-Su ChangSchool of Nutrition and Health Sciences, Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, 11031, Taipei, Taiwan.
Abel SantamariaLaboratorio de Nanotecnología y Nanomedicina, Departamento de Atención a la Salud, Universidad Autónoma Metropolitana-Xochimilco, and Facultad de Ciencias, Universidad Nacional Autónoma de México, 04960, Mexico City, Mexico.
Rongzhu LuDepartment of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Jiangsu, 212013, Zhenjiang, China.
Ji-Chang ZhouSchool of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, 518107, Shenzhen, China.
Aaron B BowmanSchool of Health Sciences, Purdue University, IN, 47907-2051, West Lafayette, USA.
Eun-Sook LeeDepartment of Pharmaceutical Sciences, Florida A&M University, FL, 32307, Tallahassee, USA.
Yousef TizabiDepartment of Pharmacology, Howard University College of Medicine, 20059, Washington, DC, USA.
Michael AschnerDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, NY, 10461, Bronx, USA. michael.aschner@einsteinmed.edu.

Funding

Mechanisms of Manganese NeurotoxicityR01ES010563 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2001 to 2025
$1.8M
Manganese exposure susceptibility as a modifier of excitotoxicity in Alzheimer's DiseaseR01ES031401 · NIEHS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Aaron B Bowman, Fiona Edith Harrison · 2022 to 2024
$1.6M
Ministry of Science and Higher Education of the Russian Federation 075-15-2024-550NIEHS NIH HHS R01 ES010563NIEHS NIH HHS R01 ES031401Shenzhen Science and Technology Innovation Program GJHZ20240218114600001
6 · The paper itself

Abstract

The objective of the present review is to discuss the involvement of altered mitochondrial quality control in Mn-induced neurotoxicity. Existing data demonstrate that mitochondrial autophagy (mitophagy) and brain mitochondrial unfolded protein response (mtUPR) are activated in response to Mn exposure to counteract the Mn-induced mitochondrial dysfunction. Both mitophagy and mtUPR have significant overlap and mechanistic intersections with the integrated stress response (ISR). Increased Mn exposures impair mitochondrial dynamics, further aggravating Mn-induced mitochondrial dysfunction. Specifically, Mn suppresses PTEN-induced kinase 1 (PINK1)-Parkin-dependent mitophagy through a variety of mechanisms, including nitric oxide synthase 2 (NOS2)-dependent PINK1 S-nitrosylation, inhibition of transcription factor EB (TFEB) signaling, and mammalian target of rapamycin complex 1 (mTORC1) activation. In addition, Mn promotes mitochondrial fission by up-regulating dynamin-1-like protein (Drp1) expression and phosphorylation via the activation of c-Jun N-terminal kinase (JNK) and inhibition of sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathways. Concomitantly, Mn impairs mitochondrial fusion by inhibiting mitofusin (Mfn) 1/2 and dynamin-like 120 kDa protein (Opa1) expression, leading to a reduction in mitochondrial size and disruption of the mitochondrial network. High-dose Mn exposure results in inhibition of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (NRF2)-dependent mitochondrial biogenesis. The latter may be mediated by inhibition of SIRT1/SIRT3 activity, as well as modulation of PINK1/ zinc finger protein 746 (ZNF746)/PGC-1α axis. Alterations in the mitochondrial quality control system may contribute to Mn-induced neuronal damage and neuroinflammation, indicating that dysregulation of the brain mitochondrial dynamics is an important mechanism by which Mn induces its neurotoxicity.

Indexed as

ManganeseMitochondriaMitophagyNeurotoxicity SyndromesAnimalsHumansMitochondrial DynamicsUnfolded Protein ResponseManganese

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.