Mitochondrial impairments in aetiopathology of multifactorial diseases: common origin but individual outcomes in context of 3P medicine

Abstract

Mitochondrial injury plays a key role in the aetiopathology of multifactorial diseases exhibiting a "vicious circle" characteristic for pathomechanisms of the mitochondrial and multi-organ damage frequently developed in a reciprocal manner. Although the origin of the damage is common (uncontrolled ROS release, diminished energy production and extensive oxidative stress to life-important biomolecules such as mtDNA and chrDNA), individual outcomes differ significantly representing a spectrum of associated pathologies including but not restricted to neurodegeneration, cardiovascular diseases and cancers. Contextually, the role of predictive, preventive and personalised (PPPM/3P) medicine is to introduce predictive analytical approaches which allow for distinguishing between individual outcomes under circumstance of mitochondrial impairments followed by cost-effective targeted prevention and personalisation of medical services. Current article considers innovative concepts and analytical instruments to advance management of mitochondriopathies and associated pathologies.

Keywords: Aetiopathology multi-organ dysfunction; Ageing; Alzheimer; Biomarker panel; COVID-19; Cancer; Cardiovascular disease; Complementary medicine; Cost efficacy; Energy imbalance; Glaucoma; Health policy; Individualised patient profiling; Injury; Liquid biopsy; Mechanisms; Mitigating measures; Mitochondrial impairment; Molecular patterns; Multi-modal diagnostics; Multifactorial disease; Neurodegeneration; Origin; Outcomes; Oxidative stress; Patient stratification; Predictive preventive personalised medicine (PPPM/3PM); ROS; Repair; Reversible damage; Suboptimal health; Vasospasm; Vicious circle.

Fig. 1

Mitochondrial function in the cell

Fig. 2

Molecular mechanisms and factors associated with mitochondrial impairments in neurodegenerative and cardiovascular diseases, and cancer. ADAM10, a disintegrin and 71 metalloprotease 10; APP, amyloid precursor protein; PSEN1, presenilin 1; PSEN2, presenilin 2; EMT, epithelial-mesenchymal transition; mtROS, mitochondrial reactive oxygen species; CVD, cardiovascular disease; DNA, deoxyribonucleic acid; ApoE, apolipoprotein E; SOD2, superoxide dismutase 2; ETC, electron transport chain; DJ1, parkin-associated protein involved with oxidative stress; HTRA2, serine peptidase 2; PD, Parkinson’s disease; mPTP, mitochondrial permeability transition pore; ATP, adenosine triphosphate; PINK1, putative serine threonine kinase; CytC, cytochrome c; ANT, adenine nucleotide translocator; CyPD, cyclophilin D; NDUFS1, anti-oxidative enzyme superoxide dismutase 2 and complex I subunit; VDAC, voltage-dependent anion channel; Parkin, E3 ubiquitin ligase; α-syn, α-synuclein; UCH-L1, ubiquitin carboxy-terminal hydrolase L1; SH3GL2, SH3 domain containing GRB2 like 2/endophilin A1