Mitochondria in heart failure

Abstract

This review focuses on the evidence accumulated in humans and animal models to the effect that mitochondria are key players in the progression of heart failure (HF). Mitochondria are the primary source of energy in the form of adenosine triphosphate that fuels the contractile apparatus, and are thus essential for the pumping activity of the heart. We evaluate changes in mitochondrial morphology and alterations in the main components of mitochondrial energetics, such as substrate utilization and oxidative phosphorylation coupled with the level of respirasomes, in the context of their contribution to the chronic energy deficit and mechanical dysfunction in HF.

Myocardial Regulation of Lipidomic Flux by Cardiolipin Synthase

“…For extraction, 2 ml of ice-cold MeOH/CHCl 3 (1:1 (v/v) with 1% acetic acid) and 2 l of antioxidant mixture (0.2 mg/ml butylated hydroxyl-toluene, 0.2 mg/ml EDTA, 2 mg/triphenylphosphine, and 2 mg/ml indomethacin in a solution of 2 4 , and 9,10-dihydroxyoctadecadienoic-d 4 in 5 l of acetonitrile) were also added at this step. The samples were immediately homogenized and subsequently vortexed several times during a 15-min incubation on ice.…”

“…The principal determinant of myocardial bioenergetic efficiency is the functional capacity of cardiac mitochondria to mediate ATP generation, substrate utilization, calcium sequestration, apoptosis, and the cellular redox state (2). Pathologic alterations in mitochondrial function, such as those that occur in diabetic myocardium, result in inefficient utilization of substrate, promoting the progression of diastolic dysfunction and heart failure (3,4). Thus, the identification of key regulatory mechanisms underlying cardiac bioenergetic dysfunction in the diabetic state is of fundamental importance to the development of novel pharmacologic targets for the treatment of diabetic cardiomyopathy.…”

“…Cardiolipin (CL) 4 is a mitochondrial specific double negatively charged phospholipid that is intricately involved in regulating diverse mitochondrial activities, such as those of Complexes I, III, IV, and V of the electron transport chain (ETC) as well as state 3 respiration and the magnitude of uncoupling, which collectively determine myocardial bioenergetic efficiency (5). In addition, CL modulates adenine nucleotide translocase activity (6,7), supercomplex formation (8,9), acyl carnitine carrier activity (10), mitochondrial fission and fusion (11), phosphate carrier and pyruvate transporter activities (12), ␣-ketoglutarate dehydrogenase activities (13), and apoptosis (14 -16).…”

A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle

“…A mutation of the cardiolipin-remodeling enzyme TAZ forms a labile supercomplex in Barth syndrome patients' cells, causing complex IV to dissociate readily from the supercomplex 17 . In various types of heart failure, excessive sympathetic stimulation may also dysregulate mitochondrial function by affecting either individual complexes or their supramolecular assemblies 18 .…”

Sterile Inflammation and Degradation Systems in Heart Failure

“…69 Mitochondria in the failing myocardium exhibit decreased activity of electron transport complexes, decreased capacity for oxidative phosphorylation and increased oxidative stress. 70 As mentioned before, when mtDNA is not completely degraded by autophagy, the remaining mtDNA induces inflammation in the heart. 3 Mitochondria in the failing myocardium also exhibit increased levels of oxidized mtDNA, reduced mtDNA replication and depletion of mtDNA.…”