A Novel Protein in Cardiac Health
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- endoplasmic reticulum
- heart failure
- mitochondrial degradation
- mitochondrial diseases
- myocardial infarction
Article, see p 2248
Heart failure is a complex disease in which the heart is unable to provide sufficient oxygenated blood for the surrounding tissues. Heart failure has emerged as an epidemic in the Western world over the past 2 decades and most often affects patients with coronary artery disease. The pathophysiology of heart failure remains unclear; however, its progression is linked to mitochondrial dysfunction.1 In support of this view, mitochondrial disorders caused by ablation of TFAM (mitochondrial transcription factor A) or ANT1 (adenine nucleotide translocator) proteins are detrimental to heart function and lead to heart failure.2,3 In this issue of Circulation, Wu et al4 show that FUNDC1 (FUN14 domain containing 1), a protein localized in the outer mitochondrial membrane, contributes to optimal cardiac function through a previously unrecognized role in the communication between mitochondria and the endoplasmic reticulum (ER). Moreover, they demonstrate that disruption of this protein function causes heart failure.
Between ≈5% and 20% of mitochondrial outer membranes are in close contact (20 nm distance) with the ER.5 Biochemically isolated in 1990 by Vance6 using a Percoll gradient centrifugation method, these ER-mitochondria contacts were described as a fraction X, which contains mitochondrial-associated ER membranes (MAMs). Recent studies document that mitochondria are in contact with the ER and that this contact plays a key role in the maintenance of organelle architecture and in overall cellular homeostasis. Thus, ER stress increases ER–mitochondria contacts, thereby promoting mitochondrial respiration and ATP synthesis.7 Moreover, ER–mitochondria contacts participate in the activation of apoptosis and in autophagosome formation.8 A relative dearth of ER–mitochondria contacts has been reported in cancer cells and in insulin-resistant cells. In contrast, an increase in ER–mitochondrial contacts has been reported in neurodegeneration. Overall, current data support the notion that these contacts …