Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(19)
Published: May 1, 2023
The
mitochondrial
electron
transport
chain
(ETC)
of
Plasmodium
malaria
parasites
is
a
major
antimalarial
drug
target,
but
critical
cytochrome
(cyt)
functions
remain
unstudied
and
enigmatic.
Parasites
express
two
distinct
cyt
c
homologs
(c
c-2)
with
unusually
sparse
sequence
identity
uncertain
fitness
contributions.
P.
falciparum
c-2
the
most
divergent
eukaryotic
homolog
currently
known
has
features
predicted
to
be
incompatible
canonical
ETC
function.
We
tagged
both
related
c1
for
inducible
knockdown.
Translational
repression
was
lethal
parasites,
which
died
from
dysfunction
impaired
ubiquinone
recycling.
In
contrast,
knockdown
or
knockout
had
little
impact
on
blood-stage
growth,
indicating
that
rely
fully
more
conserved
Biochemical
structural
studies
revealed
are
hemylated
by
holocytochrome
synthase,
UV-vis
absorbance
EPR
spectra
strongly
suggest
an
open
active
site
in
heme
stably
coordinated
only
single
axial
amino
acid
ligand
can
bind
exogenous
small
molecules.
These
provide
direct
dissection
identify
highly
molecular
adaptations
defy
role
evolution.
The FASEB Journal,
Journal Year:
2018,
Volume and Issue:
33(2), P. 1540 - 1553
Published: Sept. 17, 2018
Cytochrome
c
(Cytc)
plays
a
vital
role
in
the
mitochondrial
electron
transport
chain
(ETC).In
addition,
it
is
key
regulator
of
apoptosis.Cytc
has
multiple
other
functions
including
ROS
production
and
scavenging,
cardiolipin
peroxidation,
protein
import.Cytc
tightly
regulated
by
allosteric
mechanisms,
tissuespecific
isoforms,
post-translational
modifications
(PTMs).Distinct
residues
Cytc
are
modified
PTMs,
primarily
phosphorylations,
highly
tissue-specific
manner.These
downregulate
ETC
flux
adjust
membrane
potential
(DC
m
),
to
minimize
reactive
oxygen
species
(ROS)
under
normal
conditions.In
pathologic
acute
stress
conditions,
such
as
ischemia-reperfusion,
phosphorylations
lost,
leading
maximum
flux,
DC
hyperpolarization,
excessive
generation,
release
Cytc.It
also
dephosphorylated
form
that
leads
caspase
activation.We
discuss
complex
regulation
propose
central
regulatory
step
mammalian
can
be
rate
limiting
conditions.This
important
because
maintains
optimal
intermediate
,
generation.We
examine
phosphorylation,
acetylation,
methylation,
nitration,
nitrosylation,
sulfoxidation
consider
their
biological
significance
evaluating
stoichiometry.-Kalpage,H.
Biomedical Journal,
Journal Year:
2018,
Volume and Issue:
41(1), P. 9 - 20
Published: Feb. 1, 2018
Respiration
is
one
of
the
most
vital
and
basic
features
living
organisms.
In
mammals,
respiration
accomplished
by
respiratory
chain
complexes
located
on
mitochondrial
inner
membrane.
past
century,
scientists
put
tremendous
efforts
in
understanding
these
complexes,
but
failed
to
solve
high
resolution
structure
until
recently.
2016,
three
research
groups
reported
supercomplex
from
different
species,
fortunately
solved
our
group
has
highest
resolution.
this
review,
we
will
compare
recently
structures
respirasome,
probe
into
relationship
between
cristae
shape
organization,
discuss
highly
disputed
issues
afterwards.
Besides,
first
respirasome
medium
megacomplex
cultured
human
cells
year.
Definitely,
provide
precious
information
for
conquering
malfunction
diseases.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Aug. 16, 2022
Abstract
Nature
programs
the
structural
folding
of
an
enzyme
that
allows
its
on-demand
biofunctionality;
however,
it
is
still
a
long-standing
challenge
to
manually
modulate
enzyme’s
conformation.
Here,
we
design
exogenous
hydrogen-bonded
organic
framework
conformation
cytochrome
c,
and
hence
allow
non-native
bioactivity
for
enzyme.
The
rigid
framework,
with
net-arranged
carboxylate
inner
cage,
in
situ
installed
onto
native
c.
resultant
nano-biointerface
changes
previously
not
achieved
catalase-like
species
within
reported
c-porous
systems.
In
addition,
preserved
can
stabilize
encapsulated
channel-like
pores
also
guarantee
free
entrance
catalytic
substrates.
This
work
describes
conceptual
nanotechnology
manoeuvring
flexible
conformations
enzyme,
highlights
advantages
artificial
scaffolds
activity.
Chemical Reviews,
Journal Year:
2021,
Volume and Issue:
121(4), P. 2020 - 2108
Published: Jan. 19, 2021
This
review
focuses
on
key
components
of
respiratory
and
photosynthetic
energy-transduction
systems:
the
cytochrome
bc1
b6f
(Cytbc1/b6f)
membranous
multisubunit
homodimeric
complexes.
These
remarkable
molecular
machines
catalyze
electron
transfer
from
quinones
to
water-soluble
carriers
(such
as
cytochromes
c
or
plastocyanin),
coupling
flow
proton
translocation
across
energy-transducing
membrane
contributing
generation
a
transmembrane
electrochemical
potential
gradient,
which
powers
cellular
metabolism
in
majority
living
organisms.
Cytsbc1/b6f
share
many
similarities
but
also
have
significant
differences.
While
decades
research
provided
extensive
knowledge
these
enzymes,
several
important
aspects
their
mechanisms
remain
be
elucidated.
We
summarize
broad
range
structural,
mechanistic,
physiological
required
for
function
Cytbc1/b6f,
combining
textbook
fundamentals
with
new
intriguing
concepts
that
emerged
more
recent
studies.
The
discussion
covers
is
not
limited
(i)
energy-conserving
bifurcation
pathway
energy-wasting
superoxide
at
quinol
oxidation
site,
(ii)
mechanism
by
semiquinone
stabilized
quinone
reduction
(iii)
interactions
substrates
specific
inhibitors,
(iv)
intermonomer
role
dimeric
complex,
(v)
higher
levels
organization
regulation
involve
Cytsbc1/b6f.
In
addressing
topics,
we
point
out
existing
uncertainties
controversies,
which,
suggested,
will
drive
further
this
field.
