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Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line.

ABSTRACT: The gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurodegenerative disorders. Several studies have consistently reported a greater abundance of Akkermansia muciniphila in Parkinson disease (PD) fecal samples. Therefore, we investigated whether A.muciniphila-conditioned medium (CM) could initiate α-synuclein (αSyn) misfolding in enteroendocrine cells (EEC) - a component of the gut epithelium featuring neuron-like properties. We found that A. muciniphila CM composition is influenced by the ability of the strain to degrade mucin. Our in vitro experiments showed that the protein-enriched fraction of mucin-free CM induces RyR-mediated Ca²⁺ release and increased mitochondrial Ca²⁺ uptake leading to ROS generation and αSyn aggregation. Oral administration of A. muciniphila cultivated in the absence of mucin to mice led to αSyn aggregation in cholecystokinin (CCK)-positive EECs but no motor deficits were observed. Noteworthy, buffering mitochondrial Ca²⁺ reverted the damaging effects observed. These molecular insights offer evidence that bacterial proteins can induce αSyn aggregation in EECs.

SUBMITTER: Amorim Neto DP

PROVIDER: S-EPMC8881719 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line.

Amorim Neto Dionísio Pedro DP Bosque Beatriz Pelegrini BP Pereira de Godoy João Vitor JV Rodrigues Paulla Vieira PV Meneses Dario Donoso DD Tostes Katiane K Costa Tonoli Celisa Caldana CC Faustino de Carvalho Hernandes H González-Billault Christian C de Castro Fonseca Matheus M

iScience 20220211 3

The gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurodegenerative disorders. Several studies have consistently reported a greater abundance of Akkermansia muciniphila in Parkinson disease (PD) fecal samples. Therefore, we investigated whether A.muciniphila-conditioned medium (CM) could initiate α-synuclein (αSyn) misfolding in enteroendocrine cells (EEC) - a component of the gut epithelium featuring neuron-like properties. We found that A. ...[more]

PMID: 35243260

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Dataset Information

Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line.

Publications

<i>Akkermansia muciniphila</i> induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line.

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