Metrics of PBMCs mitochondrial function in MASLD
| MASLD outcome | Mitochondrial function metric | Key findings | Reference |
|---|---|---|---|
| MASLD (non-biopsed, diagnosed by ultrasound) | Live mitochondria-specific energy changes in PBMCs, determined by Seahorse XFp analyzer. | The real-time assessment showed reduced mitochondrial respiration capacity in PBMCs from MASLD patients. | Garrafa E, 2023 [39] |
| MASLD (simple steatosis, estimated by using the FLI score) | Mitochondrial OXPHOS capacity, determined by proteomics analysis. | Increased OXPHOS capacity with complex I + II-linked substrates in PBMCs from MASLD. | Shirakawa R, 2023 [42] |
| MASLD (diagnosed by biopsy) | Measurement of serum mitochondrial respirometry and hepatic bioenergetic profiles. | Co-presence of loss-of-function polymorphisms in PNPLA3, TM6SF2, and MBOAT7 significantly predisposes individuals to MASLD progression. | Paolini E, 2024 [63] |
| Maximal respiratory capacity. | |||
| MASLD [clinical diagnosis with at least 2 criteria (diabetes, biopsy, hypertriglyceridemia or under treatment, or CT or MRI imaging)] | Gene expression analysis related to inflammatory and metabolic pathways, determined by RNA sequencing. | The identified gene signatures showed enrichment in inflammation and metabolism pathways, suggesting their potential as diagnostic biomarkers for liver diseases. | Listopad S, 2022 [55] |
| MASLD/hepatic fibrosis (diagnosed by biopsy) | Live mitochondria-specific energy changes, determined by Seahorse XFp analyzer. | Significant reduction in mitochondrial energy consumption in PBMCs. | Ajaz S, 2021 [62] |
| MASH [diagnosed by biopsy (n = 43) or ultrasound] | mtDNA copy number as a proxy for mitochondrial mass, determined by transcriptomic analysis. | Reduced mtDNA copy number in PBMCs from MASLD patients compared to healthy subjects. | Lee AH, 2022 [41] |
| MASH (diagnosed by biopsy) | OPA1 (mitochondrial fusion marker), DRP1 (mitochondrial fission marker), and OPA1/DRP1 ratio (mitochondrial fusion/fission balance), determined by protein expression analysis by western blot. | Higher levels of OPA1 protein in MASH patients with significant fibrosis compared to those without fibrosis. Additionally, the OPA1/DRP1 ratio, indicating the balance between mitochondrial fusion and fission, was also higher in these patients. | Kunlayawutipong T, 2024 [59] |
DRP1: dynamin-related protein 1; FLI: fatty liver disease; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MBOAT7: membrane bound o-acyltransferase domain-containing 7; mtDNA: mitochondrial DNA; OPA1: optic atrophy 1; OXPHOS: oxidative phosphorylation; PBMCs: peripheral blood mononuclear cells; PNPLA3: patatin-like phospholipase domain-containing 3; RNA: ribonucleic acid; TM6SF2: transmembrane 6 superfamily member 2