Browsing by Subject "Voltage-Dependent Anion Channel 2"

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    A chemical glycoproteomics platform reveals O-GlcNAcylation of mitochondrial voltage-dependent anion channel 2.
    (Cell Rep, 2013-10-31) Palaniappan, K; Hangauer, M; Smith, T; Smart, B; Pitcher, A; Cheng, E; Bertozzi, C; Boyce, M
    Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is a critical cell signaling modality, but identifying signal-specific O-GlcNAcylation events remains a significant experimental challenge. Here, we describe a method for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated proteins and use it to identify the mitochondrial voltage-dependent anion channel 2 (VDAC2) as an O-GlcNAc substrate. VDAC2(-/-) cells resist the mitochondrial dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating a functional connection between O-GlcNAc signaling and mitochondrial physiology through VDAC2. More broadly, our method will enable the discovery of signal-specific O-GlcNAcylation events in a wide array of experimental contexts.
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    VDAC2 as a novel target for heart failure: Ca2+ at the sarcomere, mitochondria and SR.
    (Cell calcium, 2022-06) Rosenberg, Paul
    Despite a growing number of successful therapies, heart failure remains the most common cause of death and disability worldwide. Thus, new and novel therapeutic strategies are urgently needed. Mitochondria of cardiomyocytes generate ATP that is needed to power cardiac contraction. Mitochondrial-derived ATP activate myosin ATPase at the sarcomere and the sarcoplasmic reticular (SR) ATPase Ca2+ pump, both which intersect with Ca2+ during contraction. Failure to maintain the relationship between mitochondria and SR can lead to cardiomyocyte dysfunction and heart failure. Here, we discuss recent discoveries that reveal Ca2+ transport via the voltage dependent anion channel (VDAC) into the mitochondria can favorably impact cardiac contraction and prevent cardiac arrhythmias. In a broader view, discussion of the opening of a new era for HF therapeutics that will address the sarcomere, SR and mitochondria as a functional unit.