Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria

E. E. McKee, B. L. Grier, G. S. Thompson, A. C F Leung, J. D. McCourt

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best folowed by malate, succinate, and α-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; howver, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the addition of guanine nucleotide or exogenous energy-generating systems. Phosphoenolpyruvate, a component of one popular energy-generating system, was, in fact, strongly inhibitory. In summary, the results from this paper establish the substrate and nucleotide conditions optimal for heart mitochondrial protein synthesis and in addition link processes of mitochondrial metabolism to mitochondrial protein synthesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume258
Issue number3 21-3
StatePublished - 1990
Externally publishedYes

Fingerprint

Heart Mitochondria
Mitochondria
Mitochondrial Proteins
Metabolism
Adenosine Diphosphate
Adenosine Triphosphate
Proteins
Substrates
Nucleotides
Phosphoenolpyruvate
Mitochondrial Genes
Guanine Nucleotides
Adenine Nucleotides
Succinic Acid
Pyruvic Acid
Phosphorylation
Glutamic Acid
Phosphates
Hormones
Gene expression

Keywords

  • mammalian mitochondria
  • mitochondrial biogenesis
  • mitochondrial protein synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

McKee, E. E., Grier, B. L., Thompson, G. S., Leung, A. C. F., & McCourt, J. D. (1990). Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria. American Journal of Physiology - Endocrinology and Metabolism, 258(3 21-3).

Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria. / McKee, E. E.; Grier, B. L.; Thompson, G. S.; Leung, A. C F; McCourt, J. D.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 258, No. 3 21-3, 1990.

Research output: Contribution to journalArticle

McKee, EE, Grier, BL, Thompson, GS, Leung, ACF & McCourt, JD 1990, 'Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria', American Journal of Physiology - Endocrinology and Metabolism, vol. 258, no. 3 21-3.
McKee, E. E. ; Grier, B. L. ; Thompson, G. S. ; Leung, A. C F ; McCourt, J. D. / Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria. In: American Journal of Physiology - Endocrinology and Metabolism. 1990 ; Vol. 258, No. 3 21-3.
@article{cb5be6c4092345f394bed9cc90591016,
title = "Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria",
abstract = "Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best folowed by malate, succinate, and α-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; howver, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the addition of guanine nucleotide or exogenous energy-generating systems. Phosphoenolpyruvate, a component of one popular energy-generating system, was, in fact, strongly inhibitory. In summary, the results from this paper establish the substrate and nucleotide conditions optimal for heart mitochondrial protein synthesis and in addition link processes of mitochondrial metabolism to mitochondrial protein synthesis.",
keywords = "mammalian mitochondria, mitochondrial biogenesis, mitochondrial protein synthesis",
author = "McKee, {E. E.} and Grier, {B. L.} and Thompson, {G. S.} and Leung, {A. C F} and McCourt, {J. D.}",
year = "1990",
language = "English (US)",
volume = "258",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "3 21-3",

}

TY - JOUR

T1 - Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria

AU - McKee, E. E.

AU - Grier, B. L.

AU - Thompson, G. S.

AU - Leung, A. C F

AU - McCourt, J. D.

PY - 1990

Y1 - 1990

N2 - Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best folowed by malate, succinate, and α-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; howver, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the addition of guanine nucleotide or exogenous energy-generating systems. Phosphoenolpyruvate, a component of one popular energy-generating system, was, in fact, strongly inhibitory. In summary, the results from this paper establish the substrate and nucleotide conditions optimal for heart mitochondrial protein synthesis and in addition link processes of mitochondrial metabolism to mitochondrial protein synthesis.

AB - Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best folowed by malate, succinate, and α-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; howver, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the addition of guanine nucleotide or exogenous energy-generating systems. Phosphoenolpyruvate, a component of one popular energy-generating system, was, in fact, strongly inhibitory. In summary, the results from this paper establish the substrate and nucleotide conditions optimal for heart mitochondrial protein synthesis and in addition link processes of mitochondrial metabolism to mitochondrial protein synthesis.

KW - mammalian mitochondria

KW - mitochondrial biogenesis

KW - mitochondrial protein synthesis

UR - http://www.scopus.com/inward/record.url?scp=0025262019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025262019&partnerID=8YFLogxK

M3 - Article

C2 - 2316644

AN - SCOPUS:0025262019

VL - 258

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 3 21-3

ER -