Reinforcing the Evidence of Mitochondrial Dysfunction in [LC] Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach, 2024, Martínez +

Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach
Sara Martínez; Oihane E. Albóniga; María Rosa López-Huertas; Ana Gradillas; Coral Barbas

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood.

Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/−)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/−)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients.

We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Link | PDF (Journal of Proteome Research)

 

Cause or Effect?

 

Yet another paper with no stated hypothesis and unwarranted conclusion. Just poke around, find some anomaly, write paper about its grand implication so that you can put it under your belt.

 

Access to the Supplementary information is available here with no paywall
https://pubs.acs.org/doi/suppl/10.1021/acs.jproteome.3c00706/suppl_file/pr3c00706_si_001.pdf

From the supplementary information it can be seen that just like with ME/CFS metabolomics studies, ceramides (cer) are significantly altered as shown below. It's interesting that in the synthesis pathway this change in ceramides is shown to be related to sphingomyelins (SM) another metabolite that's shown up in ME/CFS studies.

 

Tess Falor on a Twitter thread about the Lisbon conference presentations reported Jonas Berquist & Chris Armstrong have been doing home and longitudinal sampling and have 3000 samples measuring 630 different metabolites with preliminary data showing low ceramides, which matches this and other studies.

 

Some introductory and concluding quotes from the paper —

 

I'll expand one of the quotes —

Those refs are —

Ceramide and the mitochondrial respiratory chain (2014, Biochimie)

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes (2021, Frontiers in Endocrinology)

Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease (2022, Biomedicines)

 

No, it's conjecture: "While it is not possible to confirm the accumulation of Cer in the mitochondria". I don't know if newer technology can or will be able to interrogate mito membrane lipid constituents. But that would open up a lot of avenues for investigation that could be of high relevance for us. Eg —

Reign in the membrane: How common lipids govern mitochondrial function
Funai; Summers; Rutter

The lipids that make up biological membranes tend to be the forgotten molecules of cell biology. The paucity of data on these important entities likely reflects the difficulties of studying and understanding their biological roles, rather than revealing a lack of importance. Indeed, the lipid composition of biological membranes has a profound impact on a diverse array of cellular processes. The focus of this review is on the effects of different lipid classes on the function of mitochondria, particularly bioenergetics, in health and disease.

Link | PubMed (Current Opinion in Cell Biology)