Role of cytochrome c heme lyase in the import of cytochrome c into mitochondria.

Nicholson, Donald W.; Hergersberg, Christoph; Neupert, Walter

doi:10.1016/s0021-9258(18)37385-x

Cited by 136 publications

(35 citation statements)

References 46 publications

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“…The direct evidence provided by the ESR experiments for the coexistence of two differently located populations of membrane-bound apocytochrome c is in accord with studies on intact mitochondria. Simultaneous accessibility of bound apocytochrome c has been found both to externally added proteases and to the heme lyase which is located in the space between the outer and inner mitochondrial membrane (Nicholson et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Membrane Location of Spin-labeled Apocytochrome c and Cytochrome c Determined by Paramagnetic Relaxation Agents

Snel¹,

Dekruijff²,

Marsh³

1994

Biochemistry

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The mitochondrial precursor protein horse heart apocytochrome c was spin-labeled on the cysteine residue at position 14 or 17 in the N-terminal region, and the mature protein yeast cytochrome c was similarly labeled on the single free cysteine residue at position 102 at the C-terminal. The proteins were bound to negatively charged phospholipid bilayers, and the accessibility of the spin-labeled cysteine residues to lipid-soluble molecular oxygen and to the lipid-impermeant chromium oxalate anion was determined from the saturation properties of the ESR spectra. Binding of the protein was found to have a considerable effect on the local oxygen concentrations within the lipid bilayer. The accessibilities of the spin-labeled proteins relative to those obtained for phospholipids spin-labeled either in the headgroup or at positions in the sn-2 acyl chain, in the presence of unlabeled protein, identify the position of the spin-labeled cysteine residues in the phospholipid bilayer. The spin label on apocytochrome c bound to phosphatidylglycerol bilayers lies between the 5- and 14-C positions of the lipid acyl chain. Admixture of > or = 75 mol % phosphatidylcholine induces an additional surface-associated apocytochrome c population. The spin label on native and heat-denatured cytochrome c is located at the membrane surface. These different extents of membrane penetration correlate also with the reduction in local oxygen concentration experienced by spin-labeled phospholipids on binding of apo- and holocytochrome c. The possible biological implications of the data are discussed.

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Section: Discussionmentioning

confidence: 99%

Membrane Location of Spin-labeled Apocytochrome c and Cytochrome c Determined by Paramagnetic Relaxation Agents

Snel¹,

Dekruijff²,

Marsh³

1994

Biochemistry

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“…It is known that the uptake of apocytochrome c is also receptor-independent (Nicholson et al, 1988;Stuart et al, 1990); however, it seems likely that the mechanism of inser-Figure 9. Presubunit Va is imported through translocation contact sites.…”

Section: Discussionmentioning

confidence: 99%

“…CS, contact sites; CYT, cytoplasm; GIP, general insertion protein; HSP 60, heat shock protein 60; lISP 70, mitochondrial heat shock protein 70; IM, inner membrane; IMS, intermembrane space; MAT, mitochondrial matrix; OM, outer membrane. tion into and across the outer membrane is different for apocytochrome c and presubunit Va. Apocytochrome c is transported across-the outer membrane in a manner that does not rely on the A~b but requires the function of cytochrome c heme lyase (Nicholson et al, 1988;Stuart et al, 1990). Presubunit Va, on the other hand, appears to follow the outer membrane protein (GIP)-contact site pathway used by many other precursor proteins (Fig.…”

Section: Discussionmentioning

confidence: 99%

An unusual mitochondrial import pathway for the precursor to yeast cytochrome c oxidase subunit Va.

Miller

Cumsky

1991

The Journal of Cell Biology

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Abstract. We have studied the import of the precursor to yeast cytochrome c oxidase subunit Va, a protein of the mitochondrial inner membrane. Like the majority of mitochondrial precursor proteins studied thus far, import of presubunit Va was dependent upon both a membrane potential (A~b) and the hydrolysis of ATE However, the levels of ATP necessary for the import of presubunit Va were significantly lower than those required for the import of a different mitochondrial precursor protein, the/~ subunit of the F,-ATPase. The rate of import of presubunit Va was found to be unaffected by temperature over the range 0 to 30°C, and was not facilitated by prior denaturation of the protein. These results, in conjunction with those of an earlier study demonstrating that presubunit Va could be efficiently targeted to mitochondria with minimal presequences, suggest that the subunit Va precursor normally exists in a loosely folded conformation. Presubunit Va could also be imported into mitochondria that had been pretreated with high concentrations of trypsin or proteinase K (1 mg/ml and 200 ttg/ml, respectively). Furthermore, the rate of import into trypsin-treated mitochondria, at both 0 and 30°C, was identical to that observed with the untreated organelles. Thus, import of presubunit Va is not dependent upon the function of a protease-sensitive surface receptor. When taken together, the results of this study suggest that presubunit Va follows an unusual import pathway. While this pathway uses several wellestablished translocation steps, in its entirety it is distinct from either the receptor-independent pathway used by apocytochrome c, or the more general pathway used by a majority of mitochondrial precursor proteins.

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“…This intermediate-sized form was accessible to proteinase K added to the intact mitochondria, indicating that part of the molecule was located outside of the outer mitochondrial membrane . The intactness of the mitochondrial membranes under the various conditions was controlled by analyzing their content of marker proteins for the intermembrane space (cytochrome b2 and cytochrome c) and the matrix (F,/6) that are known to be released or degraded upon damage of membranes (Hard et al, 1986(Hard et al, , 1987aNicholson et al ., 1988) .…”

Section: Accumulation Of the Hybrid Protein B2-dhfr In Mitochondrial Tlranslocation Contact Sites In Intact Yeast Cellsmentioning

confidence: 99%

Protein folding causes an arrest of preprotein translocation into mitochondria in vivo.

Wienhues

Becker

Schleyer

et al. 1991

The Journal of Cell Biology

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123

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Abstract. With vital yeast cells, a hybrid protein consisting of the amino-terminal third of the precursor to cytochrome b2 and of the entire dihydrofolate reductase was arrested on the import pathway into mitochondria . Accumulation of the protein in the mitochondrial membranes was achieved by inducing a stable tertiary structure of the dihydrofolate reductase domain . Thereby, three salient features of mitochondrial protein up-ROTEIN translocation across biological membranes is a key step in the biogenesis of cell organelles (Wickner and Lodish, 1985). The basic problem ofhow cy tosolically synthesized precursor proteins traverse organelle membranes was studied predominantly in cell-free systems. These systems consisted of isolated organelles, such as microsomes (ER), mitochondria, chloroplasts or peroxisomes, and precursor proteins that were synthesized in vitro or expressed in Escherichia coli and subsequently purified. With regard to mitochondria, the following steps ofprotein import have been established (for reviews see Attardi and Schatz, 1988 ;Hard and Neupert, 1990; Pfanner and Neupert,1990) . Nuclear-encoded precursor proteins are synthesized on cytosolic polysomes and targeted to specific receptors on the outer mitochondrial membrane. A loosely folded ("unfolded") conformation of a precursor protein is a prerequisite for its translocation across the mitochondrial membranes (Schleyer and Neupert, 1985;Eilers and Schatz, 1986; Chenand Douglas, 1987a) . Most precursors are translocated through contact sites between outer and inner mitochondrial membranes (translocation contact sites) . The membrane potential across the inner membrane is required for the initial entrance of a precursor into this membrane, while the completion of translocation does not depend on A0. During or after membrane translocation, the amino-terminal targeting sequence (presequence) is proteolytically cleaved off by the processing peptidase in the mitochondrial matrix .Though posttranslational translocation of unfolded precursor proteins through mitochondrial contact sites is well established in the isolated system, little is known about protein transport into mitochondria in intact cells . In early studies performed at low temperature, cytoplasmic pools of mitochondrial precursor proteins were found in Neurospora

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Role of cytochrome c heme lyase in the import of cytochrome c into mitochondria.

Cited by 136 publications

References 46 publications

Membrane Location of Spin-labeled Apocytochrome c and Cytochrome c Determined by Paramagnetic Relaxation Agents

Membrane Location of Spin-labeled Apocytochrome c and Cytochrome c Determined by Paramagnetic Relaxation Agents

An unusual mitochondrial import pathway for the precursor to yeast cytochrome c oxidase subunit Va.

Protein folding causes an arrest of preprotein translocation into mitochondria in vivo.

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