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Mitochondria: how eminent in ageing and neurodegenerative disorders?

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Abstract

Numerous factors are implicated in the onset and progression of ageing and neurodegenerative disorders, with defects in cell energy supply and free radicals regulation designated as being the main functions of mitochondria and highly accentuated in plentiful studies. Hence, analysing the role of mitochondria as one of the main factors implicated in these disorders could undoubtedly come in handy with respect to disease prevention and treatment. In this review, first, we will explore how mitochondria account for neurodegenerative disorders and ageing and later will draw the various pathways contributing to mitochondrial dysfunction in their distinct way. Also, we will discuss the deviation-countering mechanisms, particularly mitophagy, a subset of autophagy known as a much larger cellular defence mechanism and regulatory system, along with its potential therapeutic effects. Last but not least, we will be highlighting the mitochondrial transfer experiments with animal models of neurodegenerative disorders.

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Abbreviations

tra3-NPA:

3-Nitropropionic acid

6-OHDA:

6-Hydroxydopamine

AD:

Alzheimer’s disease

AKG:

α-Ketoglutarate

ALP:

Autophagy-lysosomal pathway

ALS:

Amyotrophic lateral sclerosis

ANT:

Adenine nucleotide translocator

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

Aβ:

Amyloid-β

BBD:

Bladder and bowel dysfunction

Bcl-2:

B-cell lymphoma 2

BNIP3:

Bcl2-interacting protein 3

BNIP3L:

BCL2/adenovirus E1B 19-kDa-interacting protein 3-like

BrdU:

Bromodeoxyuridine

C21orf2:

Chromosome 21 open reading frame 2

CAG:

Cytosine, adenine, guanine

CatD:

Cathepsin D

CCNF:

Cyclin F

cGAS:

Cyclic GMP-AMP synthase

CHCHD10:

Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial

CK2:

Casein kinase 2

CNS:

Central nervous system

COX:

Cytochrome c oxidase

COXIV:

COX subunit 4

CPEO:

Chronic progressive external ophthalmoplegia

CSF:

Cerebrospinal fluid

CypD:

Cyclophilin D

cyt c:

Cytochrome complex

DAT:

Dopamine transporter

DP:

Diffuse plaque

DRP1:

Dynamin-related protein 1

DUB:

Deubiquitinating enzyme

ER:

Endoplasmic reticulum

ETC:

Electron transport chain

fALS:

Familial amyotrophic lateral sclerosis

FIS1:

Fission protein 1

FUS/TLS:

Fused in sarcoma/translocated in liposarcoma

GABA:

γ-Aminobutyric acid

GLDH:

Glutamate dehydrogenase

hASC:

Human adipose-derived stem cell

HD:

Huntington’s disease

HDAC:

Histone deacetylase

HMOX2:

Haeme oxygenase 2

HSR:

Heat shock response

HTT:

Huntingtin

IMM:

Inner mitochondrial membrane

LB:

Lewy body

LIR:

LC3-interacting region

LS:

Lysosomal system

MAOB:

Monoamine oxidase B

MATR3:

Matrin 3

MBP:

Myelin basic protein

MFN1:

Mitofusins 1

MnSOD:

Manganese superoxide dismutase

MPP+ :

1-Methyl-4-phenylpyridinium

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mPTP:

Mitochondrial permeability transition pore

MS:

Multiple sclerosis

mtDNA:

Mitochondrial DNA

mtHtt:

Mutant Htt

MtMP:

Mitochondrial membrane potential

NAA:

N-acetyl aspartate

NCX:

Na+/Ca2+ exchanger

nDNA:

Nuclear DNA

NEK1:

NIMA-related kinase 1

NF:

Neurofilament

NFT:

Neurofibrillary tangle

NGF:

Nerve growth factor

NIMA:

Never in mitosis gene a

NO:

Nitric oxide

NP:

Neuritic plaque

NRF2:

Nuclear factor erythroid 2-related factor 2

OMM:

Outer mitochondrial membrane

OPA1:

Optic atrophy 1

OPTN:

Optineurin

OXPHOS:

Oxidative phosphorylation

PAS:

Pre-autophagosomal structure

PD:

Parkinson’s disease

PGAM5:

Phosphoglycerate mutase 5

PGC-1α:

PPAR-gamma coactivator 1-alpha

PINK1:

PTEN-induced kinase 1

PLP:

Proteolipid protein

PN:

Proteostasis network

polyQ:

Polyglutamate

PPAR:

Peroxisome proliferator-activated receptor

PRDX3:

Peroxiredoxin III

PRx:

Peroxiredoxin

PTM:

Post-translational modification

P-τ:

τ Protein

RIRR:

ROS-induced ROS release

RMS:

Rostral migratory stream

ROS:

Reactive oxygen species

sALS:

Sporadic amyotrophic lateral sclerosis

SNpc:

Substantia nigra pars compacta

SOD1:

Superoxide dismutase 1

Sp1:

Specificity protein 1*

STING:

Stimulator of interferon genes

TBK1:

TANK-binding kinase 1

TCE:

Trichloroethylene

TDP-43:

Transactive response DNA-binding protein 43 kDa

Trx:

Thioredoxin

TUBA4A:

Tubulin alpha-4A

Ub:

Ubiquitin

Ubl:

Ubiquitin-like

ULK1:

Unc-51-like autophagy activating kinase 1

UPP:

Ubiquitin–proteasome pathway

UPR:

Unfolded protein response

UPS:

Ubiquitin–proteasome system

VCP:

Valosin-containing protein

VDAC:

Voltage-dependent anion channel

α-syn:

α-Synuclein

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Acknowledgements

We appreciate the Burn and Research Centre members for their help in preparing this paper.

Funding

Part of this work was supported by the National Institute for Medical Research and Development (NIMAD) [Grant No. 4000519] and Guilan University of Medical Sciences [Grant No. 400032407].

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Author notes

  1. Chia Bamshad and Nima Najafi-Ghalehlou have contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran

    Chia Bamshad

  2. Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Nima Najafi-Ghalehlou

  3. Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran

    Zahra Pourmohammadi-Bejarpasi, Alireza Feizkhah, Amaneh Mohammadi Roushnadeh & Mehryar Habibi Roudkenar

  4. Department of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    Kazuo Tomita & Tomoaki Sato

  5. Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

    Yoshikazu Kuwahara

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  1. Chia Bamshad
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Contributions

CB: Investigation, Writing—Original Draft, Visualisation. NN-G: Investigation, Writing—Original Draft, Writing—Review and Editing. ZP-B: Investigation, Writing—Original Draft. KT: Writing—Review and Editing. YK: Writing—Review and Editing. TS: Writing—Review and Editing. AF: Investigation, Writing—Original Draft, Visualisation. AMR: Supervision, Visualisation, Writing—Review and Editing. MHR: Supervision, Project administration, Writing—Review and Editing.

Corresponding authors

Correspondence to Amaneh Mohammadi Roushnadeh or Mehryar Habibi Roudkenar.

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Bamshad, C., Najafi-Ghalehlou, N., Pourmohammadi-Bejarpasi, Z. et al. Mitochondria: how eminent in ageing and neurodegenerative disorders?. Human Cell 36, 41–61 (2023). https://doi.org/10.1007/s13577-022-00833-y

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