Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Abstract

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome.

Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma — a review

“…There are a series of controversies related to the parameters used in mechanical ventilation, especially when we are talking about an inflammated lung. The severe pulmonary destruction and inflammation can have severe consequences at a patient with multiple trauma, the majority leading to Multiple Organ Dysfunction Syndrome (MODS) [62,63] and death [64][65][66].…”

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

“…Although the underlying cellular events leading to MOF are incompletely understood, impaired mitochondrial function and the depletion of cellular energy stores appear to play a central role (3–5). In this study, we investigated the potential utility of using PBMCs as a proxy for measuring mitochondrial function in more vital organs such as liver, kidney and heart during hemorrhagic shock and resuscitation.…”

“…A critical component in this cascade is the development of mitochondrial dysfunction (4). Following ischemia-reperfusion, impaired mitochondrial function contributes to cell injury and organ failure by reducing aerobic ATP production and by increasing the generation of toxic free radical species (5). Mitochondrial dysfunction following hemorrhagic shock has been demonstrated in a variety of animal models and is associated with both impaired organ function and poor outcome (4,6).…”

“…Mitochondrial dysfunction following hemorrhagic shock has been demonstrated in a variety of animal models and is associated with both impaired organ function and poor outcome (4,6). Persistent mitochondrial dysfunction has also been associated with increased MOF and higher mortality in severely injured patients (3,5,7). …”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…Lancel and colleagues demonstrated in cardiomyocytes isolated 4 hours after endotoxin injection in rats, an increase in the release of caspase-3, -8, and -9-like activities, associated with destruction of the sarcomeric structure and cleavage of components of the cardiac myofilament [175]. Simvastatin, whose use has been proposed in sepsis, may protect against apoptosis induced by Staphylococcus aureus alpha-toxin [176]. …”