The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection
- 1Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 2Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
Abstract
Beyond textbook functions in homeostatic metabolism, mitochondria are now recognized as central coordinators of cell-intrinsic and cell-extrinsic immune responses to infection. Directed trafficking of proteins and other molecules between mitochondria and the rest of the cell underlies a growing catalog of these activities. Some are pro-host; others are antagonized by viral effectors or co-opted by viruses entirely. How host and viral factors rewire the mitochondrial proteome during infection to shape these outcomes remains incompletely understood. The evolutionary history of this system adds another dimension: mitochondria retain biochemical signatures of their α-proteobacterial endosymbiotic origin, and ongoing co-evolution between viral, host, and mitochondrial genomes continues to shape the proteins that traffic to and from the organelle. Using published examples, we highlight general principles, mechanisms, and consequences of host and viral protein localization to and from the mitochondria. To support discovery, we present integrated gene lists identifying host mitochondrial factors with evidence for type I interferon stimulation, interactions with viral proteins, and signatures of positive selection. Together, these resources and the principles within offer a framework for understanding mitochondria not as passive metabolic machinery but as actively contested cellular territory whose protein composition is continuously negotiated between the host and the pathogen.
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BibTeX
@article{hancks2026factory,
title = {{The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection}},
author = {Dustin C. Hancks and Steven F. Baker},
journal = {Journal of Virology},
year = {2026},
month = sep,
doi = {10.1128/jvi.01746-25},
url = {https://doi.org/10.1128/jvi.01746-25},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection
AU - Dustin C. Hancks
AU - Steven F. Baker
PY - 2026
DA - 2026/09/14
JO - Journal of Virology
DO - 10.1128/jvi.01746-25
UR - https://doi.org/10.1128/jvi.01746-25
AB - Beyond textbook functions in homeostatic metabolism, mitochondria are now recognized as central coordinators of cell-intrinsic and cell-extrinsic immune responses to infection. Directed trafficking of proteins and other molecules between mitochondria and the rest of the cell underlies a growing catalog of these activities. Some are pro-host; others are antagonized by viral effectors or co-opted by viruses entirely. How host and viral factors rewire the mitochondrial proteome during infection to shape these outcomes remains incompletely understood. The evolutionary history of this system adds another dimension: mitochondria retain biochemical signatures of their α-proteobacterial endosymbiotic origin, and ongoing co-evolution between viral, host, and mitochondrial genomes continues to shape the proteins that traffic to and from the organelle. Using published examples, we highlight general principles, mechanisms, and consequences of host and viral protein localization to and from the mitochondria. To support discovery, we present integrated gene lists identifying host mitochondrial factors with evidence for type I interferon stimulation, interactions with viral proteins, and signatures of positive selection. Together, these resources and the principles within offer a framework for understanding mitochondria not as passive metabolic machinery but as actively contested cellular territory whose protein composition is continuously negotiated between the host and the pathogen.
SN - 0022-538X
SN - 1098-5514
ER -