Table 1.

Potential targeted therapeutics which may alleviate arrhythmogenic mitochondrial dysfunction.

Mitochondria-targeted pharmacological therapy	Mechanism	Therapeutic effect
Antioxidants
TPP+ conjugated antioxidants	Highly lipophilic antioxidants conjugated to strongly positive cations accumulate in mitochondria	Reduce ROS production Reduce mitochondrial component oxidation Reduce ROS-induced apoptosis and necrosis
Szeto-Schiller peptides	Cationic tetrapeptides, accumulate in the inner mitochondrial membrane	Scavenge ROS Reduce lipid peroxidation Reduce Ca2+ induced mitochondrial swelling Reduce reperfusion injury
Modifiers of mitochondrial biogenesis
SIRT1 activators	Upregulation of SIRT1 transcription	Increasing PGC-1α expression Antioxidant properties (see above) Reduced NF-κB activation Electrophysiological modifications: Inhibition of INa−L, ICa−L Reduction of intracellular Ca2+ transients
Rapamycin	Inhibition of mTOR signaling	Reduced ROS production Reduced cardiac hypertrophy Normalization of age-related Ca2+ homeostasis disruption Increased SERCA expression Reduced RyR current amplitude Increased mitophagy

PGC-1a, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA, sarco-/endoplasmic reticulum Ca²⁺-ATPase; TPP, triphenylalkylphosphonium ion.