Proceedings of the National Academy of Sciences,
Год журнала:
2022,
Номер
119(39)
Опубликована: Сен. 19, 2022
Autophagosomes
are
unique
organelles
that
form
de
novo
as
double-membrane
vesicles
engulfing
cytosolic
material
for
destruction.
Their
biogenesis
involves
membrane
transformations
of
distinctly
shaped
intermediates
whose
ultrastructure
is
poorly
understood.
Here,
we
combine
cell
biology,
correlative
cryo-electron
tomography
(cryo-ET),
and
extensive
data
analysis
to
reveal
the
step-by-step
structural
progression
autophagosome
at
high
resolution
directly
within
yeast
cells.
The
uncovers
an
unexpectedly
thin
intermembrane
distance
dilated
phagophore
rim.
Mapping
individual
autophagic
structures
onto
a
timeline
based
on
geometric
features
reveals
dynamical
change
shape
curvature
in
growing
phagophores.
Moreover,
our
tomograms
show
organelle
interactome
autophagosomes,
highlighting
polar
organization
contact
sites
between
organelles,
such
vacuole
endoplasmic
reticulum
(ER).
Collectively,
these
findings
have
important
implications
contribution
different
sources
during
autophagy
forces
shaping
driving
phagophores
toward
closure
without
templating
cargo.
Review30
August
2021Open
Access
Autophagy
in
major
human
diseases
Daniel
J
Klionsky
orcid.org/0000-0002-7828-8118
Life
Sciences
Institute,
University
of
Michigan,
Ann
Arbor,
MI,
USA
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for
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papers
by
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author
Giulia
Petroni
Department
Radiation
Oncology,
Weill
Cornell
Medical
College,
New
York,
NY,
Ravi
K
Amaravadi
Medicine,
Pennsylvania,
Philadelphia,
PA,
Abramson
Cancer
Center,
Eric
H
Baehrecke
Molecular,
Cell
and
Biology,
Massachusetts
School,
Worcester,
MA,
Andrea
Ballabio
orcid.org/0000-0003-1381-4604
Telethon
Institute
Genetics
Pozzuoli,
Italy
Translational
Sciences,
Section
Pediatrics,
Federico
II
University,
Naples,
Molecular
Human
Genetics,
Baylor
College
Jan
Dan
Duncan
Neurological
Research
Texas
Children
Hospital,
Houston,
TX,
Patricia
Boya
orcid.org/0000-0003-3045-951X
Margarita
Salas
Center
Biological
Research,
Spanish
National
Council,
Madrid,
Spain
José
Manuel
Bravo-San
Pedro
Faculty
Physiology,
Complutense
Networked
Biomedical
Neurodegenerative
Diseases
(CIBERNED),
Ken
Cadwell
Kimmel
Biology
Medicine
at
the
Skirball
York
Grossman
School
Microbiology,
Division
Gastroenterology
Hepatology,
Langone
Health,
Francesco
Cecconi
orcid.org/0000-0002-5614-4359
Stress
Survival
Unit,
Autophagy,
Recycling
Disease
(CARD),
Danish
Society
Copenhagen,
Denmark
Pediatric
Onco-Hematology
Gene
Therapy,
IRCCS
Bambino
Gesù
Children's
Rome,
Rome
'Tor
Vergata',
Augustine
M
Choi
Pulmonary
Critical
Care
Joan
Sanford
I.
York-Presbyterian
Mary
E
Nephrology
Hypertension,
Charleen
T
Chu
orcid.org/0000-0002-5052-8271
Pathology,
Pittsburgh
Pittsburgh,
Patrice
Codogno
orcid.org/0000-0002-5492-3180
Institut
Necker-Enfants
Malades,
INSERM
U1151-CNRS
UMR
8253,
Paris,
France
Université
de
Maria
Isabel
Colombo
Laboratorio
Mecanismos
Moleculares
Implicados
en
el
Tráfico
Vesicular
y
la
Autofagia-Instituto
Histología
Embriología
(IHEM)-Universidad
Nacional
Cuyo,
CONICET-
Facultad
Ciencias
Médicas,
Mendoza,
Argentina
Ana
Cuervo
orcid.org/0000-0002-0771-700X
Developmental
Albert
Einstein
Bronx,
Aging
Studies,
Vojo
Deretic
Inflammation
Metabolism
(AIM,
Excellence,
Mexico
Health
Albuquerque,
NM,
Ivan
Dikic
orcid.org/0000-0001-8156-9511
Biochemistry
II,
Goethe
Frankfurt,
Frankfurt
am
Main,
Germany
Buchmann
Zvulun
Elazar
Biomolecular
The
Weizmann
Science,
Rehovot,
Israel
Eeva-Liisa
Eskelinen
Biomedicine,
Turku,
Finland
Gian
Fimia
orcid.org/0000-0003-4438-3325
Sapienza
Epidemiology,
Preclinical
Advanced
Diagnostics,
Infectious
'L.
Spallanzani'
IRCCS,
David
A
Gewirtz
orcid.org/0000-0003-0437-4934
Pharmacology
Toxicology,
Virginia
Commonwealth
Richmond,
VA,
Douglas
R
Green
Immunology,
St.
Jude
Memphis,
TN,
Malene
Hansen
Burnham
Prebys
Discovery
Program
Development,
Aging,
Regeneration,
La
Jolla,
CA,
Marja
Jäättelä
orcid.org/0000-0001-5950-7111
Death
Metabolism,
&
Disease,
Cellular
Terje
Johansen
orcid.org/0000-0003-1451-9578
Group,
Tromsø—The
Arctic
Norway,
Tromsø,
Norway
Gábor
Juhász
Szeged,
Hungary
Anatomy,
Eötvös
Loránd
Budapest,
Vassiliki
Karantza
Merck
Co.,
Inc.,
Kenilworth,
NJ,
Claudine
Kraft
orcid.org/0000-0002-3324-4701
ZBMZ,
Freiburg,
CIBSS
-
Centre
Integrative
Signalling
Guido
Kroemer
orcid.org/0000-0002-9334-4405
Recherche
des
Cordeliers,
Equipe
Labellisée
par
Ligue
Contre
le
Cancer,
Sorbonne
Université,
Inserm
U1138,
Universitaire
France,
Metabolomics
Platforms,
Gustave
Roussy,
Villejuif,
Pôle
Biologie,
Hôpital
Européen
Georges
Pompidou,
AP-HP,
Suzhou
Systems
Chinese
Academy
Suzhou,
China
Karolinska
Women's
Stockholm,
Sweden
Nicholas
Ktistakis
Programme,
Babraham
Cambridge,
UK
Sharad
Kumar
orcid.org/0000-0001-7126-9814
South
Australia,
Adelaide,
SA,
Australia
Carlos
Lopez-Otin
orcid.org/0000-0001-6964-1904
Departamento
Bioquímica
Biología
Medicina,
Instituto
Universitario
Oncología
del
Principado
Asturias
(IUOPA),
Universidad
Oviedo,
Centro
Investigación
Biomédica
Red
Cáncer
(CIBERONC),
Kay
F
Macleod
Ben
May
Gordon
W-338,
Chicago,
IL,
Frank
Madeo
Biosciences,
NAWI
Graz,
Austria
BioTechMed-Graz,
Field
Excellence
BioHealth
–
Jennifer
Martinez
Immunity,
Laboratory,
Environmental
NIH,
Triangle
Park,
NC,
Alicia
Meléndez
Department,
Queens
City
Flushing,
Graduate
PhD
Programs
Noboru
Mizushima
orcid.org/0000-0002-6258-6444
Tokyo,
Japan
Christian
Münz
orcid.org/0000-0001-6419-1940
Viral
Immunobiology,
Experimental
Zurich,
Switzerland
Josef
Penninger
Biotechnology
Austrian
(IMBA),
Vienna
BioCenter
(VBC),
Vienna,
British
Columbia,
Vancouver,
BC,
Canada
Rushika
Perera
orcid.org/0000-0003-2435-2273
California,
San
Francisco,
Helen
Diller
Family
Comprehensive
Mauro
Piacentini
orcid.org/0000-0003-2919-1296
"Tor
Vergata",
Laboratory
Cytology
Russian
Saint
Petersburg,
Russia
Fulvio
Reggiori
orcid.org/0000-0003-2652-2686
Cells
Systems,
Section,
Groningen,
Netherlands
C
Rubinsztein
Cambridge
Dementia
Kevin
Ryan
Beatson
Glasgow,
Junichi
Sadoshima
Cardiovascular
Rutgers
Jersey
Newark,
Laura
Santambrogio
Sandra
Edward
Meyer
Caryl
Englander
Precision
Luca
Scorrano
orcid.org/0000-0002-8515-8928
Istituto
Veneto
di
Medicina
Molecolare,
Padova,
Hans-Uwe
Simon
Pharmacology,
Bern,
Clinical
Immunology
Allergology,
Sechenov
Moscow,
Fundamental
Kazan
Federal
Kazan,
Anna
Katharina
Kennedy
Rheumatology,
NDORMS,
Oxford,
Anne
Simonsen
orcid.org/0000-0003-4711-7057
Basic
Oslo,
Reprogramming,
Oslo
Hospital
Montebello,
Alexandra
Stolz
orcid.org/0000-0002-3340-439X
Nektarios
Tavernarakis
orcid.org/0000-0002-5253-1466
Biotechnology,
Foundation
Technology-Hellas,
Heraklion,
Crete,
Greece
Sharon
Tooze
orcid.org/0000-0002-2182-3116
Francis
Crick
London,
Tamotsu
Yoshimori
orcid.org/0000-0001-9787-3788
Osaka
Suita,
Intracellular
Membrane
Dynamics,
Frontier
Integrated
Science
Division,
Open
Transdisciplinary
Initiatives
(OTRI),
Junying
Yuan
Interdisciplinary
on
Chemistry,
Shanghai
Organic
Shanghai,
Harvard
Boston,
Zhenyu
Yue
Neurology,
Friedman
Brain
Icahn
Mount
Sinai,
Qing
Zhong
orcid.org/0000-0001-6979-955X
Key
Differentiation
Apoptosis
Ministry
Education,
Pathophysiology,
Jiao
Tong
(SJTU-SM),
Lorenzo
Galluzzi
Corresponding
Author
[email
protected]
orcid.org/0000-0003-2257-8500
Dermatology,
Yale
Haven,
CT,
Pietrocola
orcid.org/0000-0002-2930-234X
Biosciences
Nutrition,
Huddinge,
mor
New England Journal of Medicine,
Год журнала:
2020,
Номер
383(16), С. 1564 - 1576
Опубликована: Окт. 14, 2020
Autophagy
is
a
complex
process
of
intracellular
degradation
senescent
or
malfunctioning
organelles.
Dysregulated
autophagy
associated
with
certain
cancers,
neurodegenerative
diseases,
immune
dysfunction,
and
aging.
Therapies
aimed
at
regulating
are
being
developed.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Апрель 4, 2022
Abstract
Traditional
drug
discovery
mainly
focuses
on
direct
regulation
of
protein
activity.
The
development
and
application
activity
modulators,
particularly
inhibitors,
has
been
the
mainstream
in
development.
In
recent
years,
PROteolysis
TArgeting
Chimeras
(PROTAC)
technology
emerged
as
one
most
promising
approaches
to
remove
specific
disease-associated
proteins
by
exploiting
cells’
own
destruction
machinery.
addition
PROTAC,
many
different
targeted
degradation
(TPD)
strategies
including,
but
not
limited
to,
molecular
glue,
Lysosome-Targeting
Chimaera
(LYTAC),
Antibody-based
PROTAC
(AbTAC),
are
emerging.
These
technologies
have
only
greatly
expanded
scope
TPD,
also
provided
fresh
insights
into
discovery.
Here,
we
summarize
advances
major
TPD
technologies,
discuss
their
potential
applications,
hope
provide
a
prime
for
both
biologists
chemists
who
interested
this
vibrant
field.
Annual Review of Cell and Developmental Biology,
Год журнала:
2021,
Номер
37(1), С. 143 - 169
Опубликована: Июнь 21, 2021
Selective
autophagy
is
the
lysosomal
degradation
of
specific
intracellular
components
sequestered
into
autophagosomes,
late
endosomes,
or
lysosomes
through
activity
selective
receptors
(SARs).
SARs
interact
with
autophagy-related
(ATG)8
family
proteins
via
sequence
motifs
called
LC3-interacting
region
(LIR)
in
vertebrates
and
Atg8-interacting
(AIMs)
yeast
plants.
can
be
divided
two
broad
groups:
soluble
membrane
bound.
Cargo
substrate
selection
may
independent
dependent
ubiquitin
labeling
cargo.
In
this
review,
we
discuss
mechanisms
mammalian
a
focus
on
unifying
principles
employed
recognition,
interaction
forming
autophagosome
LIR-ATG8
interactions,
recruitment
core
for
efficient
formation
substrate.