In many cell types, IP(3) and ryanodine receptor (IP(3)R/RyR)-mediated Ca(2+) mobilization from the sarcoendoplasmic reticulum (ER/SR) results in an elevation of mitochondrial matrix [Ca(2+)]. Although delivery of the released Ca(2+) to the mitochondria has been established as a fundamental signaling process, the molecular mechanism underlying mitochondrial Ca(2+) uptake remains a challenge for...

BACKGROUND Left ventricular assist devices (LVADs) have improved survival in patients with end-stage heart failure. Compared with previous trials, the Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial enrolled patients with more advanced heart failure and high prevalence of intravenous inotropic therapy. This study analyzes, on a post hoc basis...

BACKGROUND The mechanisms by which ischemic preconditioning (IP) inhibits mitochondrial permeability transition pore opening and, hence, ischemia-reperfusion injury remain unclear. Here we investigate whether and how mitochondria-bound hexokinase 2 (mtHK2) may exert part of the cardioprotective effects of IP. METHODS AND RESULTS Control and IP Langendorff-perfused rat hearts were subject to i...

IκBα resides in the cytosol where it retains the inducible transcription factor NF-κB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF-κB that accumulate high amounts of mitochondrial IκBα as a NF-κB target gene. 3T3 IκBα(-/-) cells also become protected from apopt...

IjBa resides in the cytosol where it retains the inducible transcription factor NF-jB. We show that IjBa also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF-jB that accumulate high amounts of mitochondrial IjBa as a NF-jB target gene. 3T3 IjBa / cells also become protected from apoptosi...

The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the follo...

Human cytomegalovirus (HCMV) encodes the UL37 exon 1 protein (pUL37x1), which is the potent viral mitochondrion-localized inhibitor of apoptosis (vMIA), to increase survival of infected cells. HCMV vMIA traffics from the endoplasmic reticulum (ER) to ER subdomains, which are physically linked to mitochondria known as mitochondrion-associated membranes (MAM), and to mitochondria. The antiapoptot...

Normal cellular lifespan is contingent upon preserving outer mitochondrial membrane (OMM) integrity, as permeabilization promotes apoptosis. BCL-2 family proteins control mitochondrial outer membrane permeabilization (MOMP) by regulating the activation of the pro-apoptotic BCL-2 effector molecules, BAX and BAK. Sustainable cellular stress induces proteins (e.g., BID, BIM, and cytosolic p53) cap...

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The accuracy of tail-anchored (TA) protein targeting to the endoplasmic reticulum (ER) depends on the Guided Entry of Tail-Anchored (Get) protein targeting machinery. The fate of TA proteins that become inappropriately inserted into other organelles, such as mitochondria, is unknown. Here, we identify Msp1, a conserved, membrane-anchored AAA-ATPase (ATPase associated with a variety of cellular ...