Mycobacterial Protein PE_PGRS30 Induces Macrophage Apoptosis Through Prohibitin 2 Mitochondrial Function Interference

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2023 Feb 13

PMID 36778852

Authors

Kazunori Matsumura

Satoshi Takaki

Teruo Kirikae

Affiliations

Soon will be listed here.

Abstract

PE_PGRS30 belongs to the PE_PGRS protein family and is characterized by a conserved Pro-Glu (PE) domain and a typically polymorphic GC-rich sequence (PGRS) domain. PE_PGRS30 is a virulence factor of that induces macrophage cell death. We found that RAW264.7 cells and murine alveolar macrophages underwent apoptosis in response to PE_PGRS30. The host protein prohibitin 2 (PHB2) was identified as a target molecule. PE_PGRS30 and PHB2 interact the PGRS domain and mitochondrial targeting sequence, respectively. PHB2 overexpression reduced macrophage apoptosis in response to PE_PGRS30. PE_PGRS30 co-localized with PHB2, not in mitochondria, but in lysosomes. The maintenance of mitochondrial structure by PHB2 was impaired in response to the PGRS domain. These results indicated that PE_PGRS30 reduces PHB2 in mitochondria, resulting in mitochondrial dysfunction and cellular apoptosis.

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