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Alzheimer’s disease alters astrocytic functions related to neuronal support and transcellular internalization of mitochondria

View ORCID ProfileRiikka Lampinen, View ORCID ProfileIrina Belaya, View ORCID ProfileLiudmila Saveleva, View ORCID ProfileJeffrey R Liddell, Dzhessi Rait, View ORCID ProfileMikko T Huuskonen, Raisa Giniatullina, Annika Sorvari, Liisi Soppela, View ORCID ProfileNikita Mikhailov, Isabella Boccuni, View ORCID ProfileRashid Giniatullin, View ORCID ProfileMarcela Cruz-Haces, View ORCID ProfileJulia Konovalova, View ORCID ProfileMarja Koskuvi, View ORCID ProfileTuomas Rauramaa, View ORCID ProfileAndrii Domanskyi, Riikka H Hämäläinen, Gundars Goldsteins, View ORCID ProfileJari Koistinaho, View ORCID ProfileTarja Malm, View ORCID ProfileSweelin Chew, View ORCID ProfileKirsi Rilla, View ORCID ProfileAnthony R White, Nicholas Marsh-Armstrong, View ORCID ProfileKatja M Kanninen
doi: https://doi.org/10.1101/2021.09.15.460570
Riikka Lampinen
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Irina Belaya
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Liudmila Saveleva
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Jeffrey R Liddell
2Department of Pharmacology & Therapeutics, University of Melbourne, Australia
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Dzhessi Rait
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Mikko T Huuskonen
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Raisa Giniatullina
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Annika Sorvari
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Liisi Soppela
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Nikita Mikhailov
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Isabella Boccuni
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Rashid Giniatullin
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Marcela Cruz-Haces
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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  • ORCID record for Marcela Cruz-Haces
Julia Konovalova
3Institute of Biotechnology, University of Helsinki, Finland
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Marja Koskuvi
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Tuomas Rauramaa
4Department of Pathology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland
5Hemorrhagic Brain Pathology Research Group, NeuroCenter, Kuopio University Hospital, Kuopio, Finland
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Andrii Domanskyi
3Institute of Biotechnology, University of Helsinki, Finland
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Riikka H Hämäläinen
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Gundars Goldsteins
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Jari Koistinaho
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
6Neuroscience Center, University of Helsinki, Finland
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Tarja Malm
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Sweelin Chew
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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Kirsi Rilla
7Institute of Biomedicine, University of Eastern Finland, Finland
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Anthony R White
8Mental Health Program, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Australia
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Nicholas Marsh-Armstrong
9Department of Ophthalmology and Vision Science, University of California Davis, USA
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Katja M Kanninen
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
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  • ORCID record for Katja M Kanninen
  • For correspondence: katja.kanninen@uef.fi
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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 and degradation of neuronal mitochondria are significantly increased in astrocytes isolated from aged AD mouse brains. We also 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 aged AD astrocytes. Significant increases in the mitophagy regulator Ambra1 were observed in the aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of aged AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 17, 2021.
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Alzheimer’s disease alters astrocytic functions related to neuronal support and transcellular internalization of mitochondria
Riikka Lampinen, Irina Belaya, Liudmila Saveleva, Jeffrey R Liddell, Dzhessi Rait, Mikko T Huuskonen, Raisa Giniatullina, Annika Sorvari, Liisi Soppela, Nikita Mikhailov, Isabella Boccuni, Rashid Giniatullin, Marcela Cruz-Haces, Julia Konovalova, Marja Koskuvi, Tuomas Rauramaa, Andrii Domanskyi, Riikka H Hämäläinen, Gundars Goldsteins, Jari Koistinaho, Tarja Malm, Sweelin Chew, Kirsi Rilla, Anthony R White, Nicholas Marsh-Armstrong, Katja M Kanninen
bioRxiv 2021.09.15.460570; doi: https://doi.org/10.1101/2021.09.15.460570
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Alzheimer’s disease alters astrocytic functions related to neuronal support and transcellular internalization of mitochondria
Riikka Lampinen, Irina Belaya, Liudmila Saveleva, Jeffrey R Liddell, Dzhessi Rait, Mikko T Huuskonen, Raisa Giniatullina, Annika Sorvari, Liisi Soppela, Nikita Mikhailov, Isabella Boccuni, Rashid Giniatullin, Marcela Cruz-Haces, Julia Konovalova, Marja Koskuvi, Tuomas Rauramaa, Andrii Domanskyi, Riikka H Hämäläinen, Gundars Goldsteins, Jari Koistinaho, Tarja Malm, Sweelin Chew, Kirsi Rilla, Anthony R White, Nicholas Marsh-Armstrong, Katja M Kanninen
bioRxiv 2021.09.15.460570; doi: https://doi.org/10.1101/2021.09.15.460570

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