Mitochondrial Homeostasis in Acute Organ Failure

Abstract

The kidneys compose approximately 0.5% of the body mass but consume about 10% of the oxygen in cellular respiration. This discordance is due to the high energy demands on the kidney for reabsorption of filtered blood components and makes the kidney sensitive to mitochondrial stress, the primary source of cellular ATP. Regardless of the etiology, acute kidney injury (AKI) almost always involves aspects of mitochondrial dysfunction. Recent evidence from experimental models suggests that preserving mitochondrial function or promoting mitochondrial repair rescues renal function during AKI. In this review we discuss the effect of AKI on disruption of mitochondrial homeostasis, and how the dynamic processes of mitochondrial biogenesis, fission/fusion, and mitophagy influence renal injury and recovery.

Rapid Renal Regulation of Peroxisome Proliferator-activated Receptor γ Coactivator-1α by Extracellular Signal-Regulated Kinase 1/2 in Physiological and Pathological Conditions

“…Inhibiting phosphorylated ERK1/2 pre-surgery attenuated the PGC-1␣ and NRF1 mRNA decreases and prevented an increase in serum creatinine. We have previously shown that PGC-1␣ is rapidly decreased following diverse models of AKI in mice and rats, and these results implicate ERK1/2 as the mediator behind this transcriptional suppression (10,11,32).…”

“…Previous studies demonstrated that rapid and persistent disruption of mitochondria homeostasis is an important contributor to the pathology of renal ischemia/reperfusion (IR) injury (10,11).…”

“…IR-induced renal injury rapidly suppresses MB, PGC-1␣, and its direct downstream targets at the transcriptional and protein level (10,11,13). However, the mechanism(s) by which PGC-1␣ is transcriptionally suppressed after injury has not been determined.…”

Proteomic approaches to the study of renal mitochondria

“…In experimental models of AKI, abnormal mitochondrial biogenesis, fission/fusion, and autophagy have been characterized and recovery of mitochondrial functions was found to be important for function of the kidney 11 . Ischemia-reperfusion injury in AKI contributes to fragmentation of mitochondria and processes leading to cell death 10 .…”

“…Dysfunction of mitochondria caused by inherited mitochondrial cytopathies or acquired defects of proteins involved in mitochondrial metabolic pathways contributes to the pathophysiology of acute and chronic renal disorders 7 . Disruption of mitochondrial energetic metabolism [7][8][9] and morphology 10,11 is recognized as important contributors to tubular dysfunction in acute kidney injury (AKI). Increased production of ROS triggered by hypoxia in mitochondria during sepsis leads to kidney dysfunction and contributes to dysfunction of organs.…”