Mitochondrial Reserve Capacity in At-Risk Populations: Untested Prospective Study

1 Background

The mitochondrial reserve threshold model (Section:mtdna-reserve-threshold in Chapter:integrative-models) proposes that inherited mtDNA haplogroup background reduces mitochondrial reserve capacity below a threshold at which an acute stressor can trigger a persistent hypometabolic state. ME/CFS has a documented heritable component (first-degree relative risk 2.70), but the mechanistic substrate is unknown. Crucially, to our knowledge no published study has measured mitochondrial reserve capacity before ME/CFS onset in any population.