# Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study

## TL;DR

This study shows that mitochondrial transplantation can restore immune cell metabolism in sepsis by reactivating key metabolic pathways.

## Contribution

The study provides direct metabolomic evidence that mitochondrial transplantation reprograms immune cell metabolism during sepsis.

## Key findings

- Sepsis suppresses amino acid, carbohydrate, and lipid metabolites like aspartic acid and myo-inositol.
- Mitochondrial transplantation partially restores these metabolites and reactivates TCA cycle and nucleotide pathways.
- Exogenous mitochondria reverse sepsis-induced metabolic suppression and promote immune cell bioenergetic recovery.

## Abstract

Sepsis induces severe immune and metabolic dysfunction driven by mitochondrial failure. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore mitochondrial bioenergetics, but its metabolic impact on immune cells remains unclear. Here, we used gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics to evaluate metabolic alterations in peripheral blood mononuclear cells (PBMCs) and splenocytes from a rat polymicrobial sepsis model treated with MT. Principal component and partial least-squares discriminant analyses revealed distinct clustering between sham, sepsis, and MT groups. Sepsis markedly suppressed metabolites related to amino acid, carbohydrate, and lipid metabolism, including aspartic acid, glutamic acid, AMP, and myo-inositol, reflecting mitochondrial metabolic paralysis. MT partially restored these metabolites toward sham levels, reactivating tricarboxylic acid (TCA) cycle, nucleotide, and lipid pathways. Pathway analysis confirmed that exogenous mitochondria reversed sepsis-induced metabolic suppression and promoted bioenergetic recovery in immune cells. These findings provide direct metabolomic evidence that MT reprograms immune metabolism and restores oxidative and biosynthetic function during sepsis, supporting its potential as a mitochondrial-based metabolic therapy.