AUTOPHAGY : MOLECULAR INSIGHTS AND EMERGING THEMES IN HUMAN

PATHOLOGY AND THERAPEUTIC STRATEGIES

Mini Project submitted to the Jawaharlal Nehru technological university Anantapur (JNTUA) in
partial fulfillment of the requirement for the award of
BACHELOR OF PHARMACY

M.Harikrishna
(REG.NO:17G41R0014)
Under the guidance of
Mr. O.Sreenivasa Krishna M.pharm.,
Academic Assistant

Oil Technological And Pharmaceutical Research Institute

(OTPRI)
(A Constituent Unit of Jawaharlal Nehru Technological University Anantapur)
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ANANTHAPURAMU-515001,A.P.,INDIA
 AUTOPHAGY- SEMINAL DISCOVERIES

Christian René Marie Joseph, Viscount de Duve (2 October 1917 – 4 May

2013) Christian de Duve was an internationally renowned cell biologist
whose serendipitous observation while investigating the workings of insulin
[
led to groundbreaking insights into the organization of the cell. The
observation, which he once described as “essentially irrelevant to the object
of our research,” ultimately led him to discover two organelles—the
lysosome and the peroxisome—for which he shared the Nobel Prize in
Physiology or Medicine in 1974 with Albert Claude and George E. Palade.

Christian de Duve (1917–2013)

[
YOSHINORI OHSUMI- MECHANISTIC INSIGHTS IN
TO AUTOPHAGY

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 AUTOPHAGY
•Introduction
•Types of autophagy
•Cellular and molecular mechanisms
•Signaling pathways
C

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 INTRODUCTION
•Auto-Self ,phagien= to eat
•Autophagy is a lysosomal degradation pathway
that is essential for survival, differentiation,
development, and homeostasis.
•Autophagy principally to protect organisms
against diverse pathologies, including
infections, cancer, neurodegeneration, aging,
and heart disease.
•Evolutionarily conserved cytoplasmic quality
control mechanism.
•Basal rate of autophagy prevents ubiquitinated
protein deposition and helps tissue
homeostasis.
•First autophagy in rat liver cells-ALEX
NOVIKOFF
•Cellular renovation strategy 5
11/10/2022 Ambati sudharshana raju,(M.pharm-pharmacology). 6
 TYPES OF AUTOPHAGY
 Macro-autophagy
Micro-autophagy
Chaperone-mediated autophagy,

General feature for all of them : proteolytic degradation

of cytosolic components in autophagosome by fusion with
the lysosome.
Autophagosome formation

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 The basic machinery of Autophagy

Initiation
•Starts from a phagophore: lipid bilayer
isolated membrane
•Contributed by the endoplasmic reticulum
(ER) and/or the trans-Golgi and endosomes
Elongation
•This phagophore expands to engulf intra-cellular cargo, such as
protein aggregates, organelles and ribosomes, thereby
sequestering the cargo in a double-membraned
autophagosome
Maturation- Degradation
The autophagosome matures and fuses with the
lysosome, promoting the degradation of
autophagosomal contents by lysosomal acid proteases
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 MACRO AUTOPHAGY

Autophagosome ( a double membrane-bound vesicle)

fuses with the lysosome to form an autolysosome.
size: 400-1500 nm

Delivers cytoplasmic cargo to the lysosome through

autophagosome (
It could be selective or non-selective

The most important type is macroautophagy

referred to as ‘autophagy”

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 Micro-autophagy

•By Invagination of the lysosome

membrane, cytosolic components are
directly taken up by the lysosome itself
through.

•It could be selective or non-selective

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Ambati sudharshana raju,(M.pharm-pharmacology).
Chaperone-mediated autophagy (CMA)

•Targeted proteins are translocated across the

lysosomal membrane in a complex with
chaperone proteins (such as Hsc-70) that are
recognized by the lysosomal membrane
receptor lysosomal-associated membrane
protein 2A (LAMP-2A), resulting in their
unfolding and degradation.

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11/10/2022 Ambati sudharshana raju,(M.pharm-pharmacology). 14
 )

Summary of functions of autophagy

11/10/2022 Ambati sudharshana raju,(M.pharm-pharmacology). 15

 The basic machinery of Autophagy

Initiation
•Starts from a phagophore: lipid bilayer
isolated membrane
•Contributed by the endoplasmic reticulum
(ER) and/or the trans-Golgi and endosomes
Elongation
•This phagophore expands to engulf intra-cellular cargo, such as
protein aggregates, organelles and ribosomes, thereby
sequestering the cargo in a double-membraned
autophagosome
Maturation- Degradation
The autophagosome matures and fuses with the
lysosome, promoting the degradation of
autophagosomal contents by lysosomal acid proteases
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11/10/2022 Ambati sudharshana raju,(M.pharm-pharmacology). 18
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AUTOPHAGY ACTIVATORS

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 CONCLUSION
Cells routinely replace their contents to stay healthy but also to make
morphological and functional changes. The process of autophagy as an
intracellular renovation systemhas been conserved throughout
evolution, and can take it as an advantage for disease therapy.

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 REFERENCES

1. de Duve, C. (2005). The lysosome turns fifty. Nat Cell Biol 7,

847–849
2. . 2. de Duve, C., Pressman, B.C., Gianetto, R., Wattiaux, R.,
and Appelmans, F. (1955) Tissue fractionation studies. 6.
Intracellular distribution patterns of enzymes in rat-liver
tissue. Biochem J 60, 604–617.
3. 3. Novikoff, A.B, Beaufay, H., and de Duve, C. (1956)
Electron microscopy of lysosome-rich fractions from rat
liver. Journal Biophys Biochem Cytol. 2, 179–190.
4. 4. Clark, S.L. (1957) Cellular differentiation in the kidneys of
newborn mice studied with the electron microscope. J
Biophys Biochem Cytol 3, 349–376.
5. 5. Novikoff, A.B. (1959) The proximal tubule cell in
experimental hydronephrosis. J Biophys Biochem Cytol 6,
136–138.
6. 6. Ashford, T.P., and Porter, K.R. (1962) Cytoplasmic
components in hepatic cell lysosomes. J Cell Biol 12, 198–
202.
7. 7. Novikoff, A.B., and Essner, E. (1962) Cytolysomes and
mitochondrial degeneration. J Cell Biol 15, 140–146.

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n k y o
T h a
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