McCommis 2015 Cell Metab

From Bioblast
Publications in the MiPMap
McCommis KS, Chen Z, Fu X, McDonald WG, Colca JR, Kletzien RF, Burgess SC, Finck BN (2015) Loss of mitochondrial pyruvate carrier 2 in the liver leads to defects in gluconeogenesis and compensation via pyruvate-alanine cycling. Cell Metab 22:682-94.

Β» PMID: 26344101 Open Access

McCommis Kyle S, Chen Zhouji, Fu Xiaorong, McDonald William G, Colca Jerry R, Kletzien Rolf F, Burgess Shawn C, Finck Brian N (2015) Cell Metab

Abstract: Pyruvate transport across the inner mitochondrial membrane is believed to be a prerequisite for gluconeogenesis in hepatocytes, which is important for the maintenance of normoglycemia during prolonged food deprivation but also contributes to hyperglycemia in diabetes. To determine the requirement for mitochondrial pyruvate import in gluconeogenesis, mice with liver-specific deletion of mitochondrial pyruvate carrier 2 (LS-Mpc2-/-) were generated. Loss of MPC2 impaired, but did not completely abolish, hepatocyte conversion of labeled pyruvate to TCA cycle intermediates and glucose. Unbiased metabolomic analyses of livers from fasted LS-Mpc2-/- mice suggested that alterations in amino acid metabolism, including pyruvate-alanine cycling, might compensate for the loss of MPC2. Indeed, inhibition of pyruvate-alanine transamination further reduced mitochondrial pyruvate metabolism and glucose production by LS-Mpc2-/- hepatocytes. These data demonstrate an important role for MPC2 in controlling hepatic gluconeogenesis and illuminate a compensatory mechanism for circumventing a block in mitochondrial pyruvate import.

Copyright Β© 2015 Elsevier Inc. All rights reserved.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US MO St Louis McCommis KS, US MO St Louis Finck B

Labels: MiParea: Respiration, mt-Membrane, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Liver  Preparation: Permeabilized cells, Isolated mitochondria 

Coupling state: OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 


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