2015/2016 autofagia

AUTOFAGIA
CORSO DI BIOLOGIA DELLO SVILUPPO
PROF. FRANCESCO CECCONI
Autofagia: Auto-Digestione
L’autofagia è un meccanismo
molto conservato
•  Dal Lievito all’uomo
•  Le prime evidenze su questo processo avvennero tramite
microscopia in lievito
MacroAutofagia:
Diversi tipi di autofagia:
Quando si attiva l’autofagia?
•  Autofagia basale: importante per l’omeostasi cellulare
(controllo di qualità e omeostasi energetica)
•  Autofagia indotta da stress:
Es.
- Deprivazione di aa o fattori di crescita
- Carenza di ossigeno (ipossia)
- Infezioni batteriche
- Danno mitocondriale
Che cosa è degradato
dall’autofagia?
  Porzioni di citoplasma
  Organelli danneggiati
  Proteine a lunga emivita
  Patogeni
  Aggregati proteici
Da dove origina l’autofagosoma?
Chi sono i protagonisti?
ATG genes: AuTophagy-related Genes
2007: Cecconi’s lab discovers a new gene
involved in autophagy: AMBRA1
Il meccanismo molecolare:
Segnali a monte:
Il principale marcatore dell’autofagia: LC3
Autofagia e morte cellulare
Autofagia e sviluppo
•  INVERTEBRATI:
During Drosophila development, autophagy is induced in response to different stimuli in different
Tissues such as fat body, intestine, salivary glands and ovary and co-operates with canonical
apoptosis to model developing tissues.
Through autophagy, cells generate a sufficient pool of aminoacids for the neosynthesis
of proteins essential for survival when the food supply is limited
•  VERTEBRATI:
1
2
3
1
FERTILIZED OOCYTE
•  After fertilization, maternal proteins in oocytes are degraded and new proteins
encoded by the zygotic genome are synthesized:
Autophagy, a process for the degradation of cytoplasmic constituents in the
lysosome, plays a critical role during this period
•  Autophagy-defective oocytes derived from oocyte-specific Atg5 (autophagyrelated 5) knockout mice failed to develop beyond the four- and eight-cell stages
if they were fertilized by Atg5-null sperm, but could develop if they were
fertilized by wild-type sperm.
2
Early neonate
•  Autophagy is induced during 3-12 h after birth in several tissues
•  Several mutant mice in ATG proteins die during this fragile
perinatal period.
In this context, autophagy has been proposed to be a source of
energy, based on the fact that these mutants show
reduced amino-acid blood levels
3
Nervous System development
•  Autophagy contributes to nervous system development at different levels.
Es. Ambra1 deficient embryos: