Mitochondrial Bioenergetics and Dynamism in the Failing Heart

Abstract

The heart is responsible for pumping blood, nutrients, and oxygen from its cavities to the whole body through rhythmic and vigorous contractions. Heart function relies on a delicate balance between continuous energy consumption and generation that changes from birth to adulthood and depends on a very efficient oxidative metabolism and the ability to adapt to different conditions. In recent years, mitochondrial dysfunctions were recognized as the hallmark of the onset and development of manifold heart diseases (HDs), including heart failure (HF). HF is a severe condition for which there is currently no cure. In this condition, the failing heart is characterized by a disequilibrium in mitochondrial bioenergetics, which compromises the basal functions and includes the loss of oxygen and substrate availability, an altered metabolism, and inefficient energy production and utilization. This review concisely summarizes the bioenergetics and some other mitochondrial features in the heart with a focus on the features that become impaired in the failing heart.

Keywords: bioenergetics; heart failure; mitochondria; mitochondrial dynamics.

Figure 1

Metabolic and mitochondrial ultrastructural changes in HF. The figure summarizes the first part of the review which reports all metabolic changes and main mitochondrial ultrastructural abnormalities accompanying HF development in humans.

Figure 2

Calcium cycling in the failing heart. The figure summarizes calcium cycling in the normal heart and how it changes in the failing heart. Proteins responsible for these alterations are highlighted in red (e.g., SERCA2a expression and molecular regulation; RyR2 aberrant gating), and the pathways to which they refer are described in the text. The importance of ATP in muscle contraction and relaxion is also depicted. On the right, a graphical abstract highlighting biogenesis and fusion-fission machinery in HF.