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Advances in Mitochondrial Dynamics and Neurodegeneration

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Biophysics".

Deadline for manuscript submissions: closed (28 April 2023) | Viewed by 17411

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Special Issue Editor

Dr. Mounia Chami

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Guest Editor

Laboratory of excellence DistALZ, Université Côte d’Azur, INSERM, CNRS, IPMC, 660 route des Lucioles, 06560 Sophia-Antipolis, Valbonne, France
Interests: mitochondria; mitophagy; endoplasmic reticulum stress; calcium signaling; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mitochondrial dynamics including fission, fusion and movement are fundamental processes that control mitochondrial function and homeostasis. Fission enables the segregation of mitochondria content and directs dysfunctional mitochondria to go through mitophagy for their degradation, while mitochondrial fusion allows the sharing of mitochondrial membrane and matrix contents. Moreover, the motility of mitochondria occurring through specific transport machinery ensures the recruitment of mitochondria at sites of high energy demand, such as the axonal and dendritic processes of neurons or at subcellular sites for their mitophagic degradation.

Destabilization of the equilibrium of mitochondrial dynamics is linked with neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases as well as amyotrophic lateral sclerosis. Moreover, mutations in the genes encoding mitochondrial fusion and fission proteins have been associated with an increasing number of genetic neurodegenerative disorders, such as Charcot–Marie–Tooth type 2A (a peripheral neuropathy) and dominant optic atrophy (an inherited optic neuropathy).

This Special Issue will be a forum for studies describing the structural and functional features of mitochondrial dynamics in neurodegenerative diseases. The Issue will include studies highlighting the impact of mitochondrial segregation, distribution, and degradation by mitophagy on normal brain cell function and the contribution of the disturbance of these processes in the development of neurodegenerative diseases. The Issue will consider studies describing technical advances to study mitochondrial dynamics and novel approaches to manipulate mitochondrial fusion, fission and movement processes

Dr. Mounia Chami
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mitochondria
fission
fusion
movement
mitophagy
neurodegeneration

Published Papers (4 papers)

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Research

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20 pages, 3401 KiB

Open AccessEditor’s ChoiceArticle

Impact of Mitochondrial A3243G Heteroplasmy on Mitochondrial Bioenergetics and Dynamics of Directly Reprogrammed MELAS Neurons

by Dar-Shong Lin, Yu-Wen Huang, Che-Sheng Ho, Tung-Sun Huang, Tsung-Han Lee, Tsu-Yen Wu, Zon-Darr Huang and Tuan-Jen Wang

Cells 2023, 12(1), 15; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12010015 - 21 Dec 2022

Cited by 4 | Viewed by 1708

Abstract

The MELAS syndrome primarily affecting the CNS is mainly caused by the m.A3243G mutation. The heteroplasmy in different tissues affects the phenotypic spectrum, yet the impact of various levels of m.A3243G heteroplasmy on CNS remains elusive due to the lack of a proper neuronal model harboring m.A3243G mutation. We generated induced neurons (iNs) through the direct reprogramming of MELAS patients, with derived fibroblasts harboring high (>95%), intermediate (68%), and low (20%) m.A3243G mutation. iNs demonstrated neuronal morphology with neurite outgrowth, branching, and dendritic spines. The heteroplasmy and deficiency of respiratory chain complexes were retained in MELAS iNs. High heteroplasmy elicited the elevation in ROS levels and the disruption of mitochondrial membrane potential. Furthermore, high and intermediate heteroplasmy led to the impairment of mitochondrial bioenergetics and a change in mitochondrial dynamics toward the fission and fragmentation of mitochondria, with a reduction in mitochondrial networks. Moreover, iNs derived from aged individuals manifested with mitochondrial fission. These results help us in understanding the impact of various heteroplasmic levels on mitochondrial bioenergetics and mitochondrial dynamics in neurons as the underlying pathomechanism of neurological manifestations of MELAS syndrome. Furthermore, these findings provide targets for further pharmacological approaches of mitochondrial diseases and validate iNs as a reliable platform for studies in neuronal aspects of aging, neurodegenerative disorders, and mitochondrial diseases. Full article

(This article belongs to the Special Issue Advances in Mitochondrial Dynamics and Neurodegeneration)

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26 pages, 8109 KiB

Open AccessArticle

A Role for PGC-1a in the Control of Abnormal Mitochondrial Dynamics in Alzheimer’s Disease

by Jia Wang, Wen-Jun Liu, Hou-Zhen Shi, Hong-Ru Zhai, Jin-Jun Qian and Wei-Ning Zhang

Cells 2022, 11(18), 2849; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11182849 - 13 Sep 2022

Cited by 8 | Viewed by 2669

Abstract

Emerging evidence suggests that the proper control of mitochondrial dynamics provides a window for therapeutic intervention for Alzheimer’s disease (AD) progression. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1 (PGC-1a) has been shown to regulate mitochondrial biogenesis in neurons. Thus far, the roles of PGC-1a in Alzheimer’s disease and its potential value for restoring mitochondrial dysfunction remain largely unknown. In the present study, we explored the impacts of PGC-1a on AD pathology and neurobehavioral dysfunction and its potential mechanisms with a particular focus on mitochondrial dynamics. Paralleling AD-related pathological deposits, neuronal apoptosis, abnormal mitochondrial dynamics and lowered membrane potential, a remarkable reduction in the expression of PGC-1a was shown in the cortex of APP/PS1 mice at 6 months of age. By infusing AAV-Ppargc1α into the lateral parietal association (LPtA) cortex of the APP/PS1 brain, we found that PGC-1a ameliorated AD-like behavioral abnormalities, such as deficits in spatial reference memory, working memory and sensorimotor gating. Notably, overexpressed PGC-1a in LPtA rescued mitochondrial swelling and damage in neurons, likely through correcting the altered balance in mitochondrial fission–fusion and its abnormal distribution. Our findings support the notion that abnormal mitochondrial dynamics is likely an important mechanism that leading to mitochondrial dysfunction and AD-related pathological and cognitive impairments, and they indicate the potential value of PGC-1a for restoring mitochondrial dynamics as an innovative therapeutic target for AD. Full article

(This article belongs to the Special Issue Advances in Mitochondrial Dynamics and Neurodegeneration)

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20 pages, 5925 KiB

Open AccessArticle

Impairment of Neuronal Mitochondrial Quality Control in Prion-Induced Neurodegeneration

by Mo-Jong Kim, Hee-Jun Kim, Byungki Jang, Hyun-Ji Kim, Mohd Najib Mostafa, Seok-Joo Park, Yong-Sun Kim and Eun-Kyoung Choi

Cells 2022, 11(17), 2744; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11172744 - 2 Sep 2022

Cited by 9 | Viewed by 3069

Abstract

Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases. Full article

(This article belongs to the Special Issue Advances in Mitochondrial Dynamics and Neurodegeneration)

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Review

Jump to: Research

42 pages, 3410 KiB

Open AccessReview

Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

by Masaru Tanaka, Ágnes Szabó, Eleonóra Spekker, Helga Polyák, Fanni Tóth and László Vécsei

Cells 2022, 11(16), 2607; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11162607 - 21 Aug 2022

Cited by 105 | Viewed by 9373

Abstract

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently, a growing number of preclinical studies have revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among others. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)–kynurenine (KYN) metabolic system, which observably contributes to the development of pathological conditions including neurological and psychiatric disorders. This review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases. Full article

(This article belongs to the Special Issue Advances in Mitochondrial Dynamics and Neurodegeneration)

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