The mitochondrial phosphate carrier: Role in oxidative metabolism, calcium handling and mitochondrial disease

Seifert, Erin L.; Ligeti, Erzsébet; Mayr, Johannes A.; Sondheimer, Neal; Hajnóczky, György

doi:10.1016/j.bbrc.2015.06.031

Cited by 59 publications

(51 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, SLC25A3 was down‐regulated with age in MA mice compared to YA or A mice (supplemental Table S1‐ Regulated proteins by age). This transporter imports free phosphate for ATP synthesis into the mitochondrial matrix using the proton motive force (Seifert et al., ). Otherwise, no mitochondrial pathways stood out as confirmed by the use of GePS and IPA.…”

Section: Resultsmentioning

confidence: 99%

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

et al. 2016

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial‐derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle‐aged mice. Susceptibility to diet‐induced obesity increased with age. Young adult and middle‐aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age‐related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat‐fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid‐derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet‐induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized.

show abstract

Section: Resultsmentioning

confidence: 99%

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These include the mitochondrial ADP/ATP carrier (ANT1; SLC25A4 ) [4], uncoupling protein (UCP1; UCP; SLC25A7 ) [5], phosphate carrier (PiC; SLC25A3 ) [6], oxoglutarate carrier (OGC; SLC25A11 ) [7], citrate carrier (CIC; SLC25A1 ) [8], and carnitine/acylcarnitine carrier (CACT; SLC25A20 ) [9]. Mutations in 14 SLC25A family members including ANT1 [10], PiC [11], CIC [12, 13], and CACT [14, 15] are now known to cause human disease [3]. Many rigorously performed biochemical studies have provided a wealth of information on mitochondrial carrier substrate selectivity [16].…”

Section: The Mitochondrial Carrier Systemmentioning

confidence: 99%

Functional Properties of the Mitochondrial Carrier System

Taylor

2017

Trends in Cell Biology

View full text Add to dashboard Cite

The mitochondrial carrier system (MCS) transports small molecules between mitochondria and the cytoplasm. It is integral to the core mitochondrial function to regulate cellular chemistry by metabolism. The mammalian MCS comprises the transporters of the 53 member canonical SLC25A family and a lesser number of identified non-canonical transporters. The recent discovery and investigations of the mitochondrial pyruvate carrier (MPC) illustrate the diverse effects a single mitochondrial carrier may exert on cellular function. However, the transport selectivities of many carriers remain unknown, and most have not been functionally investigated in mammalian cells. The mechanisms coordinating their function as a unified system remain undefined. Increased accessibility to molecular-genetic and metabolomic technologies now greatly enables investigation of the MCS. Continued investigation of the MCS may reveal how mitochondria encode complex regulatory information within chemical thermodynamic gradients. This understanding may enable precision modulation of cellular chemistry to counteract the dysmetabolism inherent in disease.

show abstract

“…Recently, human disease-associated PiC mutations were described in Turkish, Guatemalan and Haitian/Dominican families (Mayr et al, 2007(Mayr et al, , 2011Bhoj et al, 2015). Although these mutations occur in both splicing variants or only in PiC-A, further studies have not determined the functional differences between PiC-A and PiC-B (Seifert et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Tissue‐specific expression and silencing phenotypes of mitochondrial phosphate carrier paralogues in several insect species

Sugahara

Jouraku

Nakakura

et al. 2017

Insect Molecular Biology

View full text Add to dashboard Cite

The mitochondrial phosphate carrier gene (PiC) encodes a membrane protein that mediates the supply of inorganic phosphate from the cytosol into the mitochondrial matrix. This substrate-specific transport system plays an important role in efficient ATP synthesis. Mammals appear to have only one PiC with two alternative splicing variants whose functional differences remain unclear. The present study is the first to characterize the multiple genes that encode PiC in insects. Bombyx mori was found to have two PiC paralogues, one ubiquitous and one testis-specific, the latter seeming to be present only in Lepidoptera. Drosophila melanogaster was found to harbour two PiC paralogues, whereas Liriomyza chinensis, another dipteran, has three PiC paralogues. Two PiCs were found to be present in Plautia stali, and silencing either of these genes affected the normal development of P. stali nymphs, although their expression patterns differed amongst tissues. Schistocerca gregaria and Locusta migratoria have two PiC each, with different expression patterns. Tribolium castaneum was found to have only one PiC, which appears to play an essential role in larval development. Thus, although the inorganic phosphate transport system appears to be conserved across eukaryotes, PiC has become specialized in the different tissues of different insect species.

show abstract

The mitochondrial phosphate carrier: Role in oxidative metabolism, calcium handling and mitochondrial disease

Cited by 59 publications

References 74 publications

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice

Functional Properties of the Mitochondrial Carrier System

Tissue‐specific expression and silencing phenotypes of mitochondrial phosphate carrier paralogues in several insect species

Contact Info

Product

Resources

About