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Review
. 2022 Mar 7:12:835181.
doi: 10.3389/fcimb.2022.835181. eCollection 2022.

Insights Into Mitochondrial Dynamics in Chlamydial Infection

Yewei Yang  1 , Wenbo Lei  1 , Lanhua Zhao  1 , Yating Wen  1 , Zhongyu Li  1
Affiliations
Review

Insights Into Mitochondrial Dynamics in Chlamydial Infection

Yewei Yang et al. Front Cell Infect Microbiol. .

Abstract

Mitochondria are intracellular organelles that are instrumental in the creation of energy, metabolism, apoptosis, and intrinsic immunity. Mitochondria exhibit an extraordinarily high degree of flexibility, and are constantly undergoing dynamic fusion and fission changes. Chlamydia is an intracellular bacterium that causes serious health problems in both humans and animals. Due to a deficiency of multiple metabolic enzymes, these pathogenic bacteria are highly dependent on their eukaryotic host cells, resulting in a close link between Chlamydia infection and host cell mitochondria. Indeed, Chlamydia increase mitochondrial fusion by inhibiting the activation of dynein-related protein 1 (DRP1), which can regulate host cell metabolism for extra energy. Additionally, Chlamydia can inhibit mitochondrial fission by blocking DRP1 oligomerization, preventing host cell apoptosis. These mechanisms are critical for maintaining a favorable environment for reproduction and growth of Chlamydia. This review discusses the molecular mechanisms of mitochondrial fusion and fission, as well as the mechanisms by which Chlamydia infection alters the mitochondrial dynamics and the prospects of limiting chlamydial development by altering mitochondrial dynamics.

Keywords: ATP; Chlamydia; DRP1; P53; mitochondrial dynamics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the structural elements of the fission and fusion proteins. (A) Between the heptad repeat 1(HR1) and heptad repeat 2 (HR2) domains, MFN1/MFN2 have two transmembrane (TM) domains Between the HR1 and HR2 domains. (B) MFN2 contain proline rich (PR) domains in between HR1 and TM domains. (C) OPA1 have been shown to have five domains: the TM domain, the HR1 domain, the GTPase domain, the middle domain, and the GTPase effector domain (GED) domain, the mitochondrial targeting sequence(MTS) located in the N-terminal. (D) The DRP1 protein contains the following domains: the bundle signalling elements (BSE) domain, the GTPase domain, the middle domain, the variable domain (or B-insert), the GED domain.
Figure 2
Figure 2
Schematic illustration of fusion of the mitochondrial outer membrane. MFN1/2 forms dimers by linking the hydrophobic heptapeptide repeat structural domains and increases outer mitochondrial membrane cohesion through GTPase hydrolysis. After the outer membrane fusion, Mitochondria A and B can share the gap’s contents.
Figure 3
Figure 3
Schematic illustration of fusion of the mitochondrial inner membrane: OPA1’s N-terminal binds to the inner mitochondrial membrane. The membrane gap exposes the GTPase functional structural domain. In a millisecond, OPA1 completes head-tail assembly, creating membrane bending and unstable tips on the two opposing endosomes with the help of cardiolipin (CL). Preparing for endosomal fusion. When two unstable tips meet, the plasma membranes fuse, generating a small hole that connects mitochondria A and B. The contents of the two mitochondrial matrices can be exchanged.
Figure 4
Figure 4
Various phases of mitochondrial fission: (A) ER tubules bind to the outer mitochondrial membrane surface, reducing mitochondrial diameter to 150 nm. (B) DRP1 recruits to the outer mitochondrial membrane, causing its thinning. (C) GTP hydrolysis causes the mitochondrial membrane to contract, preparing the way for the next step of mitochondrial fission. (D) Mitochondria completely split.
Figure 5
Figure 5
Mechanisms by which chlamydial infection alters mitochondrial dynamics. (A) Chlamydia infects host cells and releases virulence factors through T3SS effectors, resulting in potassium efflux from the cell membrane and activation of the NADPH oxidase. This induces the production of reactive oxygen species (ROS) in the cytoplasm, which acts as a secondary signal to activate the NLRX1 protein in the outer mitochondrial membrane. The activated NLRX1 protein translocates and binds to mitochondrial complex 3, resulting in massive mitochondrial ROS production and phosphorylation of the serine residue 5 8 5 of DRP1, activating DRP1. (B) Chlamydia triggers the PI3K-ATK-HMD2 signaling pathway, which results in the ubiquitination of the P53 protein and subsequently suppresses the activation of the DRP1 protein. (C) Chlamydia increases host cell miRNA-30c-5p production, which binds to the mRNA of the P53 protein and blocks its translation, hence inhibiting DRP1 protein activation. (D) Chlamydia produces the cdu1 protein, which binds to Mcl-1 and shields it from ubiquitinated degradation, hence raising Mcl-1 protein levels and preventing DRP1 oligomerization. (E) C. pneumoniae infects host cells, resulting in mitochondria dysfunction and switch of OXPHOS to glycolysis, which enhances the bacteria growth.
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