Psoriasis and Mitochondrial Dysfunction
Yes, psoriasis is associated with dysfunctional mitochondria, as evidenced by decreased mitochondrial DNA copy number in blood cells, impaired β-oxidation, reduced expression of mitochondrial regulatory proteins in affected skin, and elevated extracellular mitochondrial DNA in serum.
Evidence of Mitochondrial Dysfunction in Psoriasis
Mitochondrial DNA Abnormalities
Mitochondrial DNA copy number (mtDNA-CN) is significantly decreased in peripheral blood cells of psoriasis patients compared to healthy controls (93.6±5.3 vs. 205±71; P = 0.04), suggesting systemic mitochondrial dysfunction 1.
Lower mtDNA-CN correlates negatively with both disease duration (r = -0.36, P = 0.006) and disease severity (r = -0.41, P = 0.003), indicating that mitochondrial dysfunction worsens as psoriasis progresses 1.
Patients with disease duration exceeding 10 years show significantly lower mtDNA-CN (74±4.3) compared to those with shorter disease duration (79±8.3, P = 0.009) 1.
Serum extracellular mtDNA is significantly elevated in psoriatic patients, with both 7s (P = 0.0496) and Cytochrome B (P = 0.0403) markers increased compared to controls, suggesting mitochondrial damage and release of mtDNA as an inflammatory trigger 2.
Impaired Mitochondrial Function in Affected Skin
Gene expression of key mitochondrial regulatory proteins is significantly reduced in lesional psoriatic skin: uncoupling protein 2 (UCP2, P = 0.0218), Dynamin-related protein 1 (Drp1, P = 0.0001), and calcineurin (P = 0.0001) are all decreased compared to non-lesional or control skin 2.
This reduced expression pattern suggests impaired keratinocyte apoptosis and dysregulated mitochondrial dynamics in psoriatic lesions 2.
Metabolic Dysfunction
Psoriasis patients demonstrate a distinctive acylcarnitine profile reflecting impaired mitochondrial β-oxidation, with differences in nine specific analytes including phenylalanine, various carnitine ratios (C0, C3, C5, C6DC, C16, C18:1OH), and amino acid ratios 3.
This altered β-oxidation pattern occurs in psoriatic patients both with and without insulin resistance, suggesting mitochondrial dysfunction is intrinsic to psoriasis rather than solely a consequence of metabolic comorbidities 3.
The acylcarnitine profile suggests increased stearoyl CoA desaturase (SCD) activity in psoriatic patients, indicating altered fatty acid metabolism at the mitochondrial level 3.
Mitochondrial DNA content in tissues is paradoxically higher in psoriasis cases than controls, though this does not differ between insulin-resistant and non-insulin-resistant psoriatic patients 3.
Clinical Implications
Pathophysiologic Mechanisms
Dysregulated mitochondria lead to reduced apoptosis in keratinocytes and extracellular secretion of mtDNA, which acts as an "innate pathogen" triggering chronic inflammation characteristic of psoriasis 2.
The chronic inflammatory state in psoriasis may be perpetuated by mitochondrial dysfunction, as damaged mitochondria release inflammatory mediators 4.
Enhanced oxidative stress and autophagy flux with decreased 20S proteasome activity have been documented in blood cells of psoriasis patients, further supporting systemic mitochondrial involvement 5.
Potential Biomarker Utility
mtDNA-CN demonstrates strong diagnostic potential with an area under the curve (AUC) of 0.84 (95% CI: 0.69-0.98; P = 0.002) for differentiating psoriasis patients from healthy controls 1.
Low mtDNA-CN may represent an early abnormality in psoriasis pathogenesis and could serve as a non-invasive blood-based biomarker for early detection 1.
Therapeutic Considerations
Inhibitors of mtDNA secretion and/or UCP2 stimulants represent potential novel treatment targets based on the mitochondrial dysfunction observed in psoriasis 2.
Restoration of mitochondrial function may be a promising therapeutic strategy, as mouse model studies have shown reversibility of certain dermatologic outcomes upon restoration of mitochondrial function 4.
Important Caveats
While the major AAD/NPF guidelines 6 do not specifically address mitochondrial dysfunction in their pathophysiology discussions—focusing instead on TH1/TH17 immune pathways, genetic factors, and comorbidities—the research evidence consistently demonstrates mitochondrial abnormalities in psoriasis. This represents an emerging area of understanding that may inform future therapeutic development but is not yet incorporated into standard clinical practice guidelines.