1,500, with a distribution from 1,000 to 3 or 4,000 Fe atoms/cage; ferritins
reconstituted in the laboratory have much more homogeneous mineral sizes see
review [Theil 1987]. When the mineral content of a ferritin protein cage is very
high, damage occurs to the cage, likely from side reactions of repeated oxidoreductase catalysis, and an insoluble mass of damaged protein forms, called hemosiderin.
In living systems, multiple mechanisms regulate both the cellular influx of iron and
the synthesis of ferritin protein cages, so that hemosiderin only forms with abnormal regulation (disease). In the laboratory, the iron content of ferritin protein cages
is controlled by the amount of ferrous iron added, which is usually up 240 for miniferritins and up to 480–1,000 for maxi-ferritins (Theil 1987; Arosio et al. 2009).
All ferritin minerals contain some phosphate, but the amount varies. For example, in animals the phosphorous content is about 12% of the iron, whereas in plants
and bacteria the phosphorous content approached 100% that of the iron (Lewin
et al. 2005). The higher phosphate content in ferritin minerals minimizes order and
leads to a more amorphous ferritin mineral. When iron minerals were reconstituted
in empty ferritin protein cages with high phosphate (P: Fe ¼ 4:1) and low phosphate (P: Fe ¼ 0:1) in the solution, the phosphate-containing minerals were more
disordered when analyzed by EXAFS, TEM, electron diffraction, and M€ ossbauer
spectroscopy, and were independent of the proteins cages, which were bacterial
(Azotobacter vinelandii or Pseudomonas aeruginosa) or animal (horse spleen) in
origin (Mann et al. 1987; Rohrer et al. 1990).
The phosphate content of prokaryote cytoplasm is higher and more variable than
the cytoplasm of eukaryotic cells, which explains the high phosphate content and
greater disorder of ferritin biominerals in bacteria (Mann et al. 1987; Rohrer et al.
1990; Wade et al. 1993; Waldo et al. 1995). In plants, the plastid is evolutionarily
related to prokaryotes and thus, even though ferritin protein is encoded in a
eukaryotic nuclear gene, it is targeted to the plastid. The high phosphate content
of plant ferritin minerals, then, is explained if the plant ferritin mineral is
synthesized by the nanocage inside the plastid (Waldo et al. 1995), rather than in
the cytoplasm where the nanocage is synthesized before transport to plastids.
Whether the phosphate content of ferritin minerals is simply a reflection of the
ambient concentration where the mineral is formed or includes phosphate storage
function, is unknown.
Order in ferritin minerals varies from microcrystalline to amorphous. The most
dramatic effect is the effect of phosphate that distinguishes animal ferritin minerals
from those of bacteria and plants, where the ferritin minerals appear to form in the
prokaryotic-derived plastids. The properties of the mineral in mitochondrial ferritins
of animal, only recently discovered and studied (Corsi et al. 2002) only at the level of
the protein, is unknown. In animal tissues, the crystallinity of the ferritin mineral
varies in different tissues and disease states (St Pierre et al. 1991). One contributing
factor is the presence of catalytically inactive subunits, the animal-specific L
subunit. Ferritins with a high L subunit content have more disordered minerals
than those with few L subunits (St Pierre et al. 1991), which may relate to the
recently detected role of the catalytically active subunits in directing nucleation and
mineralization of ferritin minerals (Turano et al. 2010) (Fig. 2.4). The underlying
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
41
reconstituted in the laboratory have much more homogeneous mineral sizes see
review [Theil 1987]. When the mineral content of a ferritin protein cage is very
high, damage occurs to the cage, likely from side reactions of repeated oxidoreductase catalysis, and an insoluble mass of damaged protein forms, called hemosiderin.
In living systems, multiple mechanisms regulate both the cellular influx of iron and
the synthesis of ferritin protein cages, so that hemosiderin only forms with abnormal regulation (disease). In the laboratory, the iron content of ferritin protein cages
is controlled by the amount of ferrous iron added, which is usually up 240 for miniferritins and up to 480–1,000 for maxi-ferritins (Theil 1987; Arosio et al. 2009).
All ferritin minerals contain some phosphate, but the amount varies. For example, in animals the phosphorous content is about 12% of the iron, whereas in plants
and bacteria the phosphorous content approached 100% that of the iron (Lewin
et al. 2005). The higher phosphate content in ferritin minerals minimizes order and
leads to a more amorphous ferritin mineral. When iron minerals were reconstituted
in empty ferritin protein cages with high phosphate (P: Fe ¼ 4:1) and low phosphate (P: Fe ¼ 0:1) in the solution, the phosphate-containing minerals were more
disordered when analyzed by EXAFS, TEM, electron diffraction, and M€ ossbauer
spectroscopy, and were independent of the proteins cages, which were bacterial
(Azotobacter vinelandii or Pseudomonas aeruginosa) or animal (horse spleen) in
origin (Mann et al. 1987; Rohrer et al. 1990).
The phosphate content of prokaryote cytoplasm is higher and more variable than
the cytoplasm of eukaryotic cells, which explains the high phosphate content and
greater disorder of ferritin biominerals in bacteria (Mann et al. 1987; Rohrer et al.
1990; Wade et al. 1993; Waldo et al. 1995). In plants, the plastid is evolutionarily
related to prokaryotes and thus, even though ferritin protein is encoded in a
eukaryotic nuclear gene, it is targeted to the plastid. The high phosphate content
of plant ferritin minerals, then, is explained if the plant ferritin mineral is
synthesized by the nanocage inside the plastid (Waldo et al. 1995), rather than in
the cytoplasm where the nanocage is synthesized before transport to plastids.
Whether the phosphate content of ferritin minerals is simply a reflection of the
ambient concentration where the mineral is formed or includes phosphate storage
function, is unknown.
Order in ferritin minerals varies from microcrystalline to amorphous. The most
dramatic effect is the effect of phosphate that distinguishes animal ferritin minerals
from those of bacteria and plants, where the ferritin minerals appear to form in the
prokaryotic-derived plastids. The properties of the mineral in mitochondrial ferritins
of animal, only recently discovered and studied (Corsi et al. 2002) only at the level of
the protein, is unknown. In animal tissues, the crystallinity of the ferritin mineral
varies in different tissues and disease states (St Pierre et al. 1991). One contributing
factor is the presence of catalytically inactive subunits, the animal-specific L
subunit. Ferritins with a high L subunit content have more disordered minerals
than those with few L subunits (St Pierre et al. 1991), which may relate to the
recently detected role of the catalytically active subunits in directing nucleation and
mineralization of ferritin minerals (Turano et al. 2010) (Fig. 2.4). The underlying
2 Maxi- and Mini-Ferritins: Minerals and Protein Nanocages
41