The biosynthesis and functional role of cardiolipin

Schlame, Michael; Rua, Diego; Greenberg, Miriam L.

doi:10.1016/s0163-7827(00)00005-9

Cited by 707 publications

(626 citation statements)

References 222 publications

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“…In mitochondrion, a small portion (about 15%) of cyt c is tightly bound to the membrane while the remainder is free or loosely bound [1,2]. The unbound cyt c participates in eT and actively prevents oxidative stress, while membrane-bound cyt c is mainly involved in cell death.…”

Section: Discussionmentioning

confidence: 99%

“…In the cellular environment the protein functions between the inner and the outer membrane of the mitochondrion, mediating electron transfer between different proteins of the respiratory chain. In healthy cells a portion of cyt c (15-20%) remains tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane [1,2]. CL-bound cyt c shows tertiary structural rearrangements, which include alteration of the heme pocket region and detachment of M80 from the sixth coordination position of the heme iron [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Sinibaldi¹,

Droghetti²,

Polticelli³

et al. 2011

Journal of Inorganic Biochemistry

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In cells a portion of cytochrome c (cyt c) (15-20%) is tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane. The CL-bound protein, which has nonnative tertiary structure, altered heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in the apoptotic process. This has attracted considerable interest in order to clarify the mechanisms governing the cyt c-CL interaction. Herein we have investigated the binding reaction of CL with the c-type cytochromes from horse heart and yeast. Although the two proteins possess a similar tertiary architecture, yeast cyt c displays lower stability and, contrary to the equine protein, it does not bind ATP and lacks pro-apoptotic activity. The study has been performed in the absence and in the presence of ATP and NaCl, two compounds that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic activity of the protein. The two proteins behave differently: while CL interaction with horse cyt c is strongly influenced by the two effectors, no effect is observed for yeast cyt c. It is noteworthy that NaCl induces dissociation of the (horse cyt c)-CL complex but has no influence on that of yeast cyt c. The differences found for the two proteins highlight that specific structural factors, such as the different local structure conformation of the regions involved in the interactions with either CL or ATP, can significantly affect the behavior of cyt c in its reaction with liposomes and the subsequent pro-apoptotic action of the protein.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Sinibaldi¹,

Droghetti²,

Polticelli³

et al. 2011

Journal of Inorganic Biochemistry

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“…CL is detected exclusively in bioenergetic membranes such as those of bacteria and mitochondria, thus providing more evidence for the endosymbiotic origin of mitochondria. The biosynthetic pathway of CL in mammals has been well described [12,13]. Briefly, CL is synthesized de novo in a four step pathway catalyzed by four mitochondrial enzymes, yielding a CL archetype.…”

Section: Cardiolipin Synthesismentioning

confidence: 99%

Cardiolipin: Setting the beat of apoptosis

2007

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Cardiolipin (CL) is a mitochondria-specific phospholipid which is known to be intimately linked with the mitochondrial bioenergetic machinery. Accumulating evidence now suggests that this unique lipid also has active roles in several of the mitochondria-dependant steps of apoptosis. CL is closely associated with cytochrome c at the outer leaflet of the mitochondrial inner membrane. This interaction makes the process of cytochrome c release from mitochondria more complex than previously assumed, requiring more than pore formation in the mitochondrial outer membrane. While CL peroxidation could be crucial for enabling cytochrome c dissociation from the mitochondrial inner membrane, cytochrome c itself catalyzes CL peroxidation. Moreover, peroxy-CL directly activates the release of cytochrome c and other apoptogenic factors from the mitochondria. CL is also directly involved in mitochondrial outer membrane permeabilization by enabling docking and activation of proapoptotic Bcl-2 proteins. It appears therefore that CL has multiple roles in apoptosis and that CL metabolism contributes to the complexity of the apoptotic process.

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“…Specific lipid components in the mitochondrial membrane have a critical role in the interaction between Bcl-2 family members and mediating the conformational changes during protein-protein interactions at the membrane surface. Indeed, the presence of cardiolipin in mitochondria plays a functional role in protein interactions (Cosentino and García-Sáez 2014;Schlame et al 2000). While the compositions listed in Table 4 are obtained from healthy cells or tissues, changes in the membrane lipid compositions during apoptosis have also been well documented (Crimi and Degli Esposti 2011;Jourdain and Martinou 2009).…”

Section: The Role Of Mitochondrial Membrane Lipids In Mompmentioning

confidence: 99%

“…Rightside When rotated 180 o , 'rear' groove is found in the red ring which includes α1 and α6 helices. Reproduced with permssion from Martinou and Youle (2011) inner membrane (MIM) (Schlame et al 2000) with only small amounts (3%) present in the MOM (Hovius et al 1990). Translocation of CL from MIM to MOM has been reported and occurs via the contact sites between the two membranes (Ardail et al 1990).…”

Section: The Role Of Mitochondrial Membrane Lipids In Mompmentioning

confidence: 99%

Mitochondrial outer membrane permeabilization: a focus on the role of mitochondrial membrane structural organization

et al. 2017

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Apoptosis is important in regulating cell death turnover and is mediated by the intrinsic and death receptor-based extrinsic pathways which converge at the mitochondrial outer membrane (MOM) leading to mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of apoptotic proteins that further activate the downstream pathway of apoptosis. Thus, tight regulation of MOMP is crucial in controlling apoptosis, and a lack of control may lead to tissue and organ malformation and the development of cancers. Despite a growing number of studies focusing on the structure and activity of the proteins involved in mediating MOMP, such as the Bcl-2 family proteins, the mechanism of MOMP is not well understood. In particular, the crucial role of the various structural properties and changes in lipid components of the MOM in mediating the recruitment and activation of different Bcl-2 proteins remains poorly understood. Furthermore, the factors that control the changes in mitochondrial membrane integrity from the initiation to the final disruption of MOM have yet to be clearly defined. In this review, we provide an overview of studies that focus on the mitochondrial membrane with a biophysical analysis of the interactions of the Bcl-2 proteins with the mitochondrial membrane.

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The biosynthesis and functional role of cardiolipin

Cited by 707 publications

References 222 publications

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Cardiolipin: Setting the beat of apoptosis

Mitochondrial outer membrane permeabilization: a focus on the role of mitochondrial membrane structural organization

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