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Mitochondrial calcium uptake 2 (MICU2)-mediated pathogenic mechanism of Listeria monocytogenes
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Haihong WU1, Lifeng YANG2, Houhui SONG1, Lingli JIANG2, Rui ZHANG3, Changyong CHENG1, Mianmian CHEN1
Acta Microbiologica Sinica | 2025, 65(10) : 4537 - 4549
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Acta Microbiologica Sinica | 2025, 65(10): 4537-4549
• Research Article •
Mitochondrial calcium uptake 2 (MICU2)-mediated pathogenic mechanism of Listeria monocytogenes
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Haihong WU1, Lifeng YANG2, Houhui SONG1, Lingli JIANG2, Rui ZHANG3, Changyong CHENG1, Mianmian CHEN1
Affiliations
  • 1Key Laboratory of Applied Biotechnology on Animal Science & Veterinary Medicine of Zhejiang Province, Zhejiang Engineering Research Center for Veterinary Diagnostics & Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, the Belt and Road International Joint Laboratory for One Health and Food Safety, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang, China
  • 2Ningbo College of Health Sciences, Ningbo, Zhejiang, China
  • 3College of Veterinary Medicine, China Agricultural University, Beijing, China
Published: 2025-09-04 doi: 10.13343/j.cnki.wsxb.20250216
Outline
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[Objective] To investigate the molecular mechanism by which Listeria monocytogenes regulates the expression of mitochondrial calcium uptake 2 (MICU2) through the virulence factor listeriolysin O (LLO) and their interaction, thereby affecting mitochondrial calcium homeostasis and bacterial intracellular proliferation. [Methods] Western blotting was employed to analyze MICU2 expression in HeLa cells infected with L. monocytogenes EGD-e or Δhly. Gene silencing and eukaryotic overexpression approaches were used to examine how MICU2 regulated the intracellular proliferation of L. monocytogenes. AlphaFold3 was used to predict the interaction sites between LLO and MICU2, and co-immunoprecipitation (Co-IP) was performed to verify their interaction. Mitochondrial calcium fluorescence probe (Rhod-2 AM) was used to analyze the regulatory role of MICU2 in calcium homeostasis. [Results] EGD-e infection upregulated MICU2 expression at 4 h and 6 h post-infection (P<0.001), whereas Δhly showed no effect (P>0.05). The silencing of MICU2 enhanced bacterial proliferation (P<0.01) and elevated mitochondrial calcium levels (P<0.05), whereas overexpression of MICU2 reduced bacterial proliferation (P<0.01) and decreased mitochondrial calcium levels (P<0.05). AlphaFold3 predicted that alanine (Ala) at position 462 of LLO interacted with glutamate (Glu) at position 119 of MICU2 via a hydrogen bond, and Co-IP confirmed their interaction. [Conclusion] L. monocytogenes upregulates MICU2 expression via LLO, and MICU2 inhibits bacterial intracellular proliferation by reducing mitochondrial calcium levels. The interaction between LLO and MICU2 is a key molecular basis for this process. These findings provide insights into the pathogenic mechanism of L. monocytogenes.

Listeria monocytogenes  /  mitochondrial calcium uptake 2 (MICU2)  /  mitochondria  /  calcium homeostasis  /  infection
Haihong WU, Lifeng YANG, Houhui SONG, Lingli JIANG, Rui ZHANG, Changyong CHENG, Mianmian CHEN. Mitochondrial calcium uptake 2 (MICU2)-mediated pathogenic mechanism of Listeria monocytogenes[J]. Acta Microbiologica Sinica, 2025 , 65 (10) : 4537 -4549 . DOI: 10.13343/j.cnki.wsxb.20250216
Funding
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  • the National Key Research and Development Program of China(2023YFD1801800)
  • the Ningbo Natural Science Foundation(2023J241)
Appendix
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Year 2025 volume 65 Issue 10
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127
53
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Article Info
doi: 10.13343/j.cnki.wsxb.20250216
  • Receive Date：2025-03-18
  • Online Date：2025-11-03
  • Published：2025-09-04
Article Data
Affiliations
History
  • Received：2025-03-18
  • Accepted：2025-05-09
Funding
the National Key Research and Development Program of China(2023YFD1801800)
the Ningbo Natural Science Foundation(2023J241)
Affiliations
    1Key Laboratory of Applied Biotechnology on Animal Science & Veterinary Medicine of Zhejiang Province, Zhejiang Engineering Research Center for Veterinary Diagnostics & Advanced Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, the Belt and Road International Joint Laboratory for One Health and Food Safety, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang, China
    2Ningbo College of Health Sciences, Ningbo, Zhejiang, China
    3College of Veterinary Medicine, China Agricultural University, Beijing, China

Corresponding:

E-mail: CHEN Mianmian,
CHENG Changyong,
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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