The Role of Bacteria-Mitochondria Communication in the Activation of Neuronal Innate Immunity: Implications to Parkinson's Disease

• Autor(a) principal: Magalhães, João Duarte
• Data de Publicação: 2023
• Outros Autores: Esteves, A. Raquel, Candeias, Emanuel, Silva, Diana F. F., Empadinhas, Nuno, Cardoso, Sandra Morais
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Texto Completo: https://hdl.handle.net/10316/113931; https://doi.org/10.3390/ijms24054339
• topic: mitochondria; alphaproteobacteria; innate immunity; antimicrobial peptides; α-Synuclein; Humans; Mitochondria; Immunity, Innate; Alarmins; Bacteria; Neurons; Parkinson Disease

Mitochondria play a key role in regulating host metabolism, immunity and cellular homeostasis. Remarkably, these organelles are proposed to have evolved from an endosymbiotic association between an alphaproteobacterium and a primitive eukaryotic host cell or an archaeon. This crucial event determined that human cell mitochondria share some features with bacteria, namely cardiolipin, N-formyl peptides, mtDNA and transcription factor A, that can act as mitochondrial-derived damage-associated molecular patterns (DAMPs). The impact of extracellular bacteria on the host act largely through the modulation of mitochondrial activities, and often mitochondria are themselves immunogenic organelles that can trigger protective mechanisms through DAMPs mobilization. In this work, we demonstrate that mesencephalic neurons exposed to an environmental alphaproteobacterium activate innate immunity through toll-like receptor 4 and Nod-like receptor 3. Moreover, we show that mesencephalic neurons increase the expression and aggregation of alpha-synuclein that interacts with mitochondria, leading to their dysfunction. Mitochondrial dynamic alterations also affect mitophagy which favors a positive feedback loop on innate immunity signaling. Our results help to elucidate how bacteria and neuronal mitochondria interact and trigger neuronal damage and neuroinflammation and allow us to discuss the role of bacterial-derived pathogen-associated molecular patterns (PAMPs) in Parkinson's disease etiology.