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Cited by 97Autophagy in Disease and TherapyAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

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Lampinen, Riikka, Belaya, Irina, Saveleva, Liudmila, Liddell, Jeffrey R., Rait, Dzhessi, Huuskonen, Mikko T., Giniatullina, Raisa, Sorvari, Annika +17 more·2022·Neurobiology of Disease
DOI 10.1016/j.nbd.2022.105753
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Abstract

Under physiological conditions in vivo astrocytes internalize and degrade neuronal mitochondria in a process called transmitophagy. Mitophagy is widely reported to be impaired in neurodegeneration but it is unknown whether and how transmitophagy is altered in Alzheimer's disease (AD). Here we report that the internalization of neuronal mitochondria is significantly increased in astrocytes isolated from AD mouse brains. We also demonstrate that the degradation of neuronal mitochondria by astrocytes is increased in AD mice at the age of 6 months onwards. Furthermore, we demonstrate for the first time a similar phenomenon between human neurons and AD astrocytes, and in murine hippocampi in vivo. The results suggest the involvement of S100a4 in impaired mitochondrial transfer between neurons and AD astrocytes together with significant increases in the mitophagy regulator and reactive oxygen species in aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.

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  • 5×FAD mice exhibit abnormal neuron-astrocyte transmitophagy, characterized by increased degradation of neuronal mitochondria by astrocytes.

    “Notably, 5 × FAD mice exhibit abnormal neuron–astrocyte transmitophagy, characterized by an increased degradation of neuronal mitochondria by astrocytes [15].”

    From Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease (2025) · cites this paper as [15]

    Results §3.1 (p. 5) report increased degradation of neuronal mitochondria by astrocytes harvested from 6- and 11-month-old 5xFAD mice in co-culture. The same passage reports no change in young astrocytes, so the unqualified claim about 5xFAD mice omits an important age restriction; the measured increase was in co-culture, not a quantified increase in intact mice. (LLM, conf=0.84)

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Cited by

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Authors
Lampinen, R., Belaya, I., Saveleva, L., Liddell, J. R., Rait, D., Huuskonen, M. T., Giniatullina, R., Sorvari, A., Soppela, L., Mikhailov, N., Boccuni, I., Giniatullin, R., Cruz-Haces, M., Konovalova, J., Koskuvi, M., Domanskyi, A., Hämäläinen, R. H., Goldsteins, G., Koistinaho, J., Malm, T., Chew, S., Rilla, K., White, A. R., Marsh-Armstrong, N., & Kanninen, K. M.
Affiliations
  • University of Eastern Finland (FI)
  • The University of Melbourne (AU)
  • University of Helsinki (FI)
  • University of California, Davis (US)
Corresponding author
Kanninen, Katja M.
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2022-08
Volume
170
Pages
105753
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2022.105753
OpenAlex
W4280536568
Cited by
97
References
7
Citations by year
2026: 21 · 2025: 24 · 2024: 30 · 2023: 18 · 2022: 4
FWCI
13.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
Itä-Suomen Yliopisto
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, astrocytes, neuronal mitochondria, mitochondrial transfer, mitophagy, S100A4, reactive oxygen species, hippocampus, neurodegeneration
MeSH terms
Alzheimer Disease, Animals, Astrocytes, Neurons, Amyloid beta-Peptides, Mice, Mitophagy

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