Mitochondrial Fusion Mediated by Mitofusin 1 Regulates Macrophage Mycobactericidal Activity by Enhancing Autophagy.
Infect Immun
; 89(11): e0030621, 2021 10 15.
Article
em En
| MEDLINE
| ID: mdl-34370506
ABSTRACT
A mitochondrion, as a highly dynamic organelle, continuously changes morphology and position during its life cycle. Mitochondrial dynamics, including fission and fusion, play a critical role in maintaining functional mitochondria for ATP production, which is directly linked to host defense against Mycobacterium tuberculosis infection. However, how macrophages regulate mitochondrial dynamics during M. tuberculosis infection remains elusive. In this study, we found that M. tuberculosis infection induced mitochondrial fusion by enhancing the expression of mitofusin 1 (MFN1), which resulted in increased ATP production. Silencing of MFN1 inhibited mitochondrial fusion and subsequently reduced ATP production, which, in turn, severely impaired macrophages' mycobactericidal activity by inhibiting autophagy. Impairment of mycobactericidal activity and autophagy was replicated using oligomycin, an inhibitor of ATP synthase. In summary, our study revealed that MFN1-mediated mitochondrial fusion is essential for macrophages' mycobactericidal activity through the regulation of ATP-dependent autophagy. The MFN1-mediated metabolism pathway might be a target for the development of a host direct therapy (HDT) strategy against tuberculosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Tuberculose
/
Proteínas de Transporte da Membrana Mitocondrial
/
Dinâmica Mitocondrial
/
GTP Fosfo-Hidrolases
/
Macrófagos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article