Mitokondrie Complex V er dysreguleret hos ME patienter

I mitokondrierne bliver vores mad omsat til energi i form af ATP. Dette sker via citronsyre cyklus og de fem mitokondrie komplekser. Basis viden om dette kan læses i wikipedia. Her ses citronsyre cyklus og de fem komplekser:


Figur fra Wikipedia: Oxidative phosphorylation
https://en.wikipedia.org/wiki/Oxidative_phosphorylation

I øverste venstre hjørne ses ATP synthase også kaldet complex V. Complex V sætter en fosfat-gruppe på ADP, så der dannes ATP. Complex V er yderligere beskrevet i Wikipedia: ATP synthase:  https://en.wikipedia.org/wiki/ATP_synthase

Professor Paul Fisher fra La Trobe Universitet har anvendt Seahorse teknologi til at undersøge mitokondrier fra ME patienter. Han har vist, at ved belastning arbejder complex V ineffektivt. Når cellerne ikke er belastede kan ATP produktionen følge med, men ved belastning går det galt. Effekten af complex V er nedsat med cirka 25% - mere hos de mest syge og mindre hos de mere raske ME patienter.

Complex V dysreguleringen medfører, at de andre mitokondrie komplekser arbejder mere for at prøve at kompensere. 

Professor Paul Fisher har fremlagt sine forskningsresultater i en præsentation:

Conclusions from Paul Fisher's "Specific Mitochondrial Respiratory Defects & Compensatory Changes in ME/CFS Patient Cells":

• ATP synthesis by Complex V is less efficient in ME/CFS cells
• Nonmitochondrial O2 consumption (metabolism) and mitochondrial respiratory capacity are elevated in ME/CFS cells
• Respiration abnormalities correlate with disease state
• Proteins involved in transporting molecules across the mitochondrial membrane and in mitochondrial fatty acid oxidation are upregulated in ME/CFS cells
• TOR Complex I activity is elevated in ME/CFS lymphoblasts and could be responsible for upregulation of mitochondrial proteins
• ME/CFS cells may be less able to respond to additional acute energy demands because they have already "turned up" their capacity as much as possible
• Cause-effect relationships need to be determined

Her er link til præsentationen:
Specific Mitochondrial Respiratory Defects & Compensatory Changes in ME/CFS Patient Cells

https://www.youtube.com/watch?v=SjK39QCPeeY

Bloggen Health Rising har skrevet om præsentationen:

Emerging Insights #II: “The Cellular Equivalent of Chronic Fatigue” Found in ME/CFS

https://www.healthrising.org/blog/2019/07/18/cellular-equivalent-chronic-fatigue-mitochondria-found/

Artikel af Daniel Missailidis, Sarah Annesley og Paul Fisher
Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
https://www.preprints.org/manuscript/201907.0196/v1

Hvis du vil vide mere om ATP synthase (complex V), så er her er review fra 2019:
ATP Synthase: Structure, Function and Inhibition

https://www.degruyter.com/view/j/bmc.2019.10.issue-1/bmc-2019-0001/bmc-2019-0001.xml