Mark Wefers Bettink

Mind the mitochondria! 2 21 and alterations at the cellular and mitochondrial level we need tools that allow us to look beyond the microcirculation, probing directly aspects of cellular metabolism. Ultimately, the clinician should have access to bedside tools that enable monitoring and verification of treatment success at the microcirculatory, cellular and mitochondrial level. Such tools are currently being developed and tested both in the laboratory and in clinical trials. In this review, we will briefly discuss mitochondrial function, adaptation, causes of dysfunction, the concepts of cytopathic hypoxia and loss of hemodynamic coherence. We will briefly discuss ways to look at the mitochondria in the clinical setting, with a special focus on the novel COMET device. The COMET allows, at the bedside, direct measurement of mitochondrial oxygenation and respiration by an optical technique. Aspects of mitochondrial function Mitochondria are double-membrane organelles found in almost all cell types, with the exception of erythrocytes. One of the main functions of mitochondria is to generate adenosine triphosphate (ATP) through oxidative phosphorylation. Over the last two decades, mitochondrial research has undergone a renaissance. Apart from its role in cell bioenergetics, a whole series of discoveries revealed mitochondrial roles in cell death, disease pathology, aging, thermogenesis, oxidative stress, cell signaling and cellular regulation. A review series about the role of mitochondria in aging and various pathophysiological states has been recently published elsewhere(1). The following paragraphs will only provide a short overview of mitochondrial function. Mitochondria are the primary consumers of oxygen and are responsible for approximately 98% of total body oxygen consumption. Oxygen is ultimately used at complex IV of the electron transport chain in the inner mitochondrial membrane. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2), generated in the Krebs cycle, are transferred from carrier molecules to the electron transport chain on complex I and II respectively. The resulting electron transport through the chain causes protons to be pumped to the intermembrane space. This proton pumping causes an electrochemical potential over the inner membrane that is used to convert adenosine diphosphate (ADP) to ATP by ATP synthase. ATP is the energy currency of the cells and used for driving cellular processes like maintaining membrane potentials, protein synthesis and replication. The coupling of mitochondrial respiration to ATP production is not 100% and this leads in part to oxidative phosphorylation generating not only ATP but also reactive oxygen