Frataxin Is Localized to Both the Chloroplast and Mitochondrion and Is Involved in Chloroplast Fe-S Protein Function in Arabidopsis

Abstract

Frataxin plays a key role in eukaryotic cellular iron metabolism, particularly in mitochondrial heme and iron-sulfur (Fe-S) cluster biosynthesis. However, its precise role has yet to be elucidated. In this work, we studied the subcellular localization of Arabidopsis frataxin, AtFH, using confocal microscopy, and found a novel dual localization for this protein. We demonstrate that plant frataxin is targeted to both the mitochondria and the chloroplast, where it may play a role in Fe-S cluster metabolism as suggested by functional studies on nitrite reductase (NIR) and ferredoxin (Fd), two Fe-S containing chloroplast proteins, in AtFH deficient plants. Our results indicate that frataxin deficiency alters the normal functioning of chloroplasts by affecting the levels of Fe, chlorophyll, and the photosynthetic electron transport chain in this organelle.

Retracted: Cucumber metal tolerance protein 7 (CsMTP7) is involved in the accumulation of Fe in mitochondria under Fe excess

“…They form cage‐like structures able to bind and release approximately 4500 Fe 3+ ions in a finely controlled fashion (Arosio et al ., ; Briat et al ., ). Frataxin is a conserved iron chaperone involved in the delivery of Fe for heme biosynthesis and for ISC assembly (Babcock et al ., ; Corsi et al ., ; Turowski et al ., ). Yeast frataxin monomers can self‐assemble in vitro in the presence of Fe 2+ , yielding ferritin‐like particles of 24 or 48 subunits with physical features that are consistent with a role in Fe storage (Gakh et al ., ).…”

Roles and maturation of iron–sulfur proteins in plastids

“…Except for a few organisms like Z. mays , there is usually a single gene coding for frataxin (FH) in plants. While frataxin was believed for a long time to be exclusively located in mitochondria, it was recently reported that A. thaliana FH (AtFH) and two isoforms from Z. mays may have a dual targeting into both mitochondria and plastids [ 34 , 35 ]. According to this possible chloroplastic localization , Arabidopsis FH -deficient plants show a decrease in the heme content [ 36 ].…”

“…According to this possible chloroplastic localization , Arabidopsis FH -deficient plants show a decrease in the heme content [ 36 ]. Moreover, they present a decrease in the total chlorophyll content, in the levels of two plastidial FDXs and in nitrite reductase (NIR, a siroheme-containing enzyme) activity which could explain the observed changes in the rate of the photosynthetic electron transport chain [ 35 ]. The impact on heme content would be in good agreement with the described interaction between yeast frataxin and ferrochelatase, the terminal enzyme of heme synthesis performing porphyrin metalation [ 37 ].…”

Iron-Sulfur Cluster Complex Assembly in the Mitochondria of Arabidopsis thaliana

“…Frataxin is required to sustain the Fe–S cluster synthesis rate under environmental oxygen pressure. Additionally, decreased levels of frataxin triggers Fe deficiency responses and Fe accumulation in different organisms like yeast [ 21 , 62 ], flies [ 63 ], Arabidopsis [ 32 , 64 ], and humans [ 65 , 66 ], although it is not clear if this is a primary or secondary event. Indeed, there is a link between iron, oxygen, and frataxin, and the increased attenuation of the Fenton reaction by the AtFH-AtNFS1-AtISD11 complex is suggestive of the biological relevance of the reaction, and its relation with some of the molecular function of frataxin.…”

“…Several functions were proposed in which frataxin would be involved, including iron homeostasis and respiration [ 21 ], heme metabolism [ 22 ], assembly of Fe-S centers [ 23 , 24 ], oxidative phosphorylation and oxidative stress [ 25 ], storage of Fe in mitochondria in a water-soluble and non-toxic form [ 21 , 26 ], and recently, its involvement in persulfide transfer [ 27 ]. Previously, we described the presence of frataxin from Arabidopsis [ 24 , 28 ] and maize [ 29 , 30 ] and the results indicate that it is an essential protein in plants, required for optimal activity of Fe-S proteins and it is also involved in protection against oxidative damage [ 24 , 28 , 31 , 32 , 33 ]. It has been suggested that frataxin would participate in specific steps of the ISC pathway or heme synthesis, where the protein would act as an iron chaperone or donor [ 9 , 19 , 34 , 35 , 36 ], as a positive regulator of cysteine desulfurase in humans [ 37 ] or as an activator of the persulfide transfer [ 26 ].…”