Mitochondrial Signaling: Forwards, Backwards, and In Between

Whelan, Sean; Zuckerbraun, Brian S.

doi:10.1155/2013/351613

Cited by 73 publications

(50 citation statements)

References 86 publications

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“…No Ccp1 was detected in nuclei isolated from 2-d cells but ∼10% was reproducibly detected in 7-d nuclei (Fig. 1C) and may function as a retrograde messenger (20) (Discussion). Ccp1, like Ccp1-GFP (Fig.…”

Section: W191fmentioning

confidence: 79%

“…Ccp1 is not present in the deletion mutant to transmit a stress signal to Skn7, which regulates the expression of many antioxidant enzymes, including cytosolic Ctt1 (46,47). Hence, reverse translocation of apoCcp1 to the nucleus provides a retrograde message (20) vital in the cell's response to exogenous H 2 O 2 , a process that merits further investigation. …”

Section: Discussionmentioning

confidence: 99%

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Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria

Kathiresan

Martins

English

2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance We provide to our knowledge the first in vivo and in vitro evidence for H 2 O 2 -triggered heme transfer between proteins. Specifically, H 2 O 2 binds to and labilizes cytochrome c peroxidase (Ccp1)’s heme by oxidizing the proximal Fe ligand (His175), which activates Ccp1 to transfer its heme to apoCta1, and apoCcp1 subsequently escapes from mitochondria. This sequence of H 2 O 2 -activated heme labilization, heme transfer between proteins, and protein relocalization defines a previously undefined mechanism of H 2 O 2 signaling in cells. In contrast, established H 2 O 2 signaling mechanisms are dominated by thiol-based redox changes.

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Section: W191fmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria

Kathiresan

Martins

English

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…76 Integration of mitochondrial functions within the cell depends on anterograde and retrograde signaling pathways. 77,78 Anterograde regulation arranges signals from external and internal stimuli at the nucleus to activate genetic programs in order to adjust the mitochondrial function accordingly. Retrograde regulation includes diverse, poorly known communication pathways from mitochondria to the nucleus that influence cellular activities in response to changes in the functional state of mitochondria.…”

Section: Mitochondrial-trna Modification Pathwaysmentioning

confidence: 99%

Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading NNA/NNG triplets of 2-codon boxes

Armengod¹,

et al. 2014

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“…In addition to their roles in heme biogenesis and energy metabolism, they influence nuclear gene expression through mechanisms collectively known as "retrograde signaling" (12). This mode of signaling is implicated in disparate biological processes, including development and aging, and its deregulation contributes to a variety of diseases associated with mitochondrial dysfunction (13). The significance of this signaling in erythropoiesis is not known.…”

mentioning

confidence: 99%

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

Davuluri

Song

Liu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are the site of iron utilization, wherein imported iron is incorporated into heme or iron-sulfur clusters. Previously, we showed that a cytosolic siderophore, which resembles a bacterial siderophore, facilitates mitochondrial iron import in eukaryotes, including zebrafish. An evolutionarily conserved 3-hydroxy butyrate dehydrogenase, 3-hydroxy butyrate dehydrogenase 2 (Bdh2), catalyzes a rate-limiting step in the biogenesis of the eukaryotic siderophore. We found that inactivation of bdh2 in developing zebrafish embryo results in heme deficiency and delays erythroid maturation. The basis for this erythroid maturation defect is not known. Here we show that bdh2 inactivation results in mitochondrial dysfunction and triggers their degradation by mitophagy. Thus, mitochondria are prematurely lost in bdh2-inactivated erythrocytes. Interestingly, bdh2-inactivated erythroid cells also exhibit genomic alterations as indicated by transcriptome analysis. Reestablishment of bdh2 restores mitochondrial function, prevents premature mitochondrial degradation, promotes erythroid development, and reverses altered gene expression. Thus, mitochondrial communication with the nucleus is critical for erythroid development. T he zebrafish (Danio rerio) is a well-established model system to study vertebrate hematopoiesis: zebrafish hematopoiesis is strikingly similar to mammalian hematopoiesis, and zebrafish have inherent experimental advantages (1). In the zebrafish embryo, hematopoiesis occurs in spatially distinct steps: the primitive or first wave of hematopoiesis occurs in two distinct anatomical locations, the posterior lateral mesoderm, which forms the intermediate cell mass (ICM) and is the site of erythroid development, and the anterior lateral mesoderm, which is the site of myeloid development. The definitive or second wave of hematopoiesis arises from self-renewing hematopoietic stem cells located in the wall of dorsal aorta (2, 3). These two waves of hematopoiesis are tightly controlled at the transcriptional level (4, 5).In erythropoiesis, pluripotent hematopoietic stem cells give rise to committed erythroid progenitor cells and to additional progenitors and precursors (6). The earliest committed erythroid progenitor is the burst-forming unit erythroid, which differentiates to produce CFU-erythroid (7). Terminal erythropoiesis begins at this stage and involves as many as six terminal divisions, differential regulation of erythroid-specific genes, nuclear changes, and extrusion of mitochondria (all species) and the nucleus (mammals) (6). Terminal erythropoiesis involves predominantly three cell types: proerythroblasts, basophilic erythroblasts, and polychromatophilic erythroblasts, which undergo morphologically distinguishable pattern of differentiation (8). In terminal erythropoiesis, polychromatophilic/orthochromatophilic erythroblasts give rise to reticulocytes. Reticulocytes lose all of their organelles, including mitochondria (8). The primary method used to eliminate mitochondria is mitophagy, a form of ...

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Mitochondrial Signaling: Forwards, Backwards, and In Between

Cited by 73 publications

References 86 publications

Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria

Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria

Modification of the wobble uridine in bacterial and mitochondrial tRNAs reading NNA/NNG triplets of 2-codon boxes

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

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