Mitochondrial Dysfunction and Organ Failure in Sepsis

Sepsis is characterised by a dysregulated host response to infection that culminates in life-threatening organ dysfunction. Central to this process is mitochondrial dysfunction, which impairs cellular energy production, promotes oxidative stress and disrupts organ-specific homeostasis. In sepsis, mitochondrial respiratory complexes may become uncoupled or inhibited, leading to reduced ATP generation and accumulation of reactive oxygen species. Concurrently, failure of mitochondrial biogenesis and quality-control pathways prevents effective recovery of organelle function. These bioenergetic derangements contribute to multiorgan failure by compromising the metabolic demands of critical organs such as the heart, kidney, brain and skeletal muscle. Restoration of mitochondrial integrity has therefore emerged as a promising therapeutic strategy aimed at reducing oxidative injury, re-establishing energy balance and improving patient outcomes in sepsis.

Research from Nature Portfolio

One seminal study demonstrated that sepsis induces long-term metabolic and mitochondrial impairment in skeletal muscle satellite cells, undermining muscle regeneration and strength. Engraftment of mesenchymal stem cells reduced pro-inflammatory cytokine levels, revitalised mitochondrial respiratory capacity and restored metabolic function in satellite cells, leading to improved muscle repair. This work highlights the interplay between systemic inflammation, organ-specific stem-cell dysfunction and mitochondrial health, and suggests that cell-based therapies can target mitochondrial pathways to prevent long-term morbidity after sepsis.

Mitochondrial Dysfunction and Organ Failure in Sepsis publication trend

The graph below shows the total number of articles in mitochondrial dysfunction and organ failure in sepsis across all publications each year (not limited to Nature Index journals).

Technical terms

Mitochondrial dysfunction: Impairment of organelle processes required for ATP production, redox balance and metabolic regulation.

Oxidative stress: State in which excessive reactive oxygen species overwhelm cellular antioxidant defences, damaging lipids, proteins and DNA.

Mitochondrial biogenesis: Generation of new mitochondria through coordinated transcriptional and translational programmes to restore energy capacity.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, including superoxide and hydrogen peroxide, that can damage cellular components.

Autophagy: Cellular recycling mechanism by which damaged organelles, including mitochondria, are sequestered and degraded in lysosomes.

Satellite cells: Quiescent muscle stem cells responsible for post-injury regeneration, highly dependent on mitochondrial metabolism for activation and differentiation.

References

1. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. Nature Communications (2015).
2. An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway. Journal of Translational Medicine (2023).
3. DJ-1 Deficiency Protects against Sepsis-Induced Myocardial Depression. Antioxidants (2023).
4. Sepsis is associated with mitochondrial DNA damage and a reduced mitochondrial mass in the kidney of patients with sepsis-AKI. Critical Care (2021).