Reactome | VDAC1 transports PYR from cytosol to mitochondrial intermembrane space

VDAC1 transports PYR from cytosol to mitochondrial intermembrane space

Stable Identifier

R-HSA-9012374

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial intermembrane space, mitochondrial outer membrane

ReviewStatus

5/5

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VDAC1 transports PYR from cytosol to mitochondrial intermembrane space

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Like other ions and metabolites, pyruvate (PYR) probably crosses the outer mitochondrial membrane through the relatively non-specific, voltage-dependent anion-selective channel protein 1 (VDAC1). The channel is in a high-conductance, moderately anion-selective state at low membrane potentials (McCommis & Finck, 2015; Najbauer et al., 2022). VDAC1 is inhibited by NO (Cheng et al., 2011). It is unknown if VDAC1 needs to be in the open state to pass PYR. However, humans with defective VDAC1 show impaired PYR oxidation and ATP production (Huizing et al. 1996). The role of VDAC1 in mitochondrial dysfunction and disease was reviewed in Varughese et al., 2021.

Literature References

PubMed ID	Title	Journal	Year
8726225	Deficiency of the voltage-dependent anion channel: a novel cause of mitochondriopathy Huizing, M, Ruitenbeek, W, Thinnes, FP, DePinto, V, Wendel, U, Trijbels, FJ, Smit, LM, ter Laak, HJ, van den Heuvel, LP	Pediatr. Res.	1996
25748677	Mitochondrial pyruvate transport: a historical perspective and future research directions McCommis, KS, Finck, BN	Biochem. J.	2015
21156174	Biphasic effect of nitric oxide on the cardiac voltage-dependent anion channel Cheng, Q, Sedlic, F, Pravdic, D, Bosnjak, ZJ, Kwok, WM	FEBS Lett	2011
34359907	The Role of Voltage-Dependent Anion Channel in Mitochondrial Dysfunction and Human Disease Varughese, JT, Buchanan, SK, Pitt, AS	Cells	2021
35164499	Structure and Gating Behavior of the Human Integral Membrane Protein VDAC1 in a Lipid Bilayer Najbauer, EE, Tekwani Movellan, K, Giller, K, Benz, R, Becker, S, Griesinger, C, Andreas, LB	J Am Chem Soc	2022