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. , Ph.D.
19-12-2016
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"suicide bags, "suicide sacs,


3
1955- Biochemistry Journal 60:604-617; 1955
Christian de Duve (Belgian biologist, 1917-2013)
( Nobel / 1974, A. Claude G. Palade
)



. glucose-6-phosphatase

-
: (
)

only when considered as part of a system


involved directly or indirectly in intracellular
digestion does the term lysosome describe a
physiological unit,

4

25nm-1m

Golgi

(.)


(, )

6
pH (pH 4,5-5,0)

+ (v-)

V

( F).

7
435 (
)

40 ( )
pH
.
(1)
(2) M pH 7,2


12 (+) 2 1 (+) 2

-
( ):

8
100 :

M : LAMPs (Lysosome-associated membrane proteins)


, ()
( )

: .
LAMPs

: aa
Y:
(, , : )
9

:
, ,

1) :

2) :

( )
1) ( )
2) (, )

1) -
2) -
3)

10

1.
2.
3.
4.

/:


( . ):

(. ):

11
:



( )

12


( ( )
)
: , : ,
,
(, & )
: 0.1-0.2 m (150nm) /: 1-2 m


13




, -

-




14
+
: -
(
) (
)

:
1) ( Ganley IG. Biochemical Society
) Essays Biochem 55:65; 2013
2)
( -
)

( ,
)
,
TGN
.

,
:

15

( )


:

: 1% /
: 100% 30min


video2 video1

16
2.

M-, , ,
.
( )-
( , ,
, ) (/ )
(
(ruffles),


: -
-

()
200nm-5m




Lim and Gleeson Immunology and Cell Biology 89:836; 2011

17
2.

,


(
)

18

MHC class-II

TCR CD4+ -

19
1. ( )

2% (, 1min)

20%

20
1.

:
100nm
,


( -
)



( dynamin, synaptojanin )

( : )

21
1.


)
adaptins

2)


22
1.

.
(1g /, . )

: 10 min

1)
2)

23

TGN

: AT -V +
.
pH



???


1)
()
(
-

)

2) pH

.

24

(
+ )
+

25
:

1. :

( )




( )


( )

2. /
(
)
DNA

Predescu S A et al. Am J Physiol Lung Cell Mol Physiol 2007;293:L823-L842 26


:

3. : (
)

()

, DM,

27
3.

, , ,

Video7

1)
2)

(-)
(, )
28


(Rab5 Rab7)

29
3.



( )


: ()

30
3.

:
.

, PS

eat-me dont eat me signals

Video 5
31
3.

32
3. -

RBCs

1011

RBCs IgG C3

33
3. -

Electron micrographs of the splenic specimens examined by TEM.

C: Three phagocytized spherocytes (Sph) by a macrophage in the spleen.


D: Red cells (R), which are phagocytized, are partially digested in the cyt of macrophage.
N: nucleus.

34

https://www.youtube.com/watch?v=lam7btcxnY0

Video 4
35

36

. , ,
.

2016 , ,
, Yoshinori Ohsumi
,
.

,
.

, Ohsumi
, 2004. '80
Aaron Ciechanover, Avram Hershko Irwin Rose
. ,
. ,

, .

37
. Ohsumi
,
.
, ,
,
.

,
.
.
, 1974 Christian de Duve.

,
. ,
,
.

, , 2, .


,
,
.
38

Christian de Duve 1963



(, , , , , , )

1) - (
)

: (
)
t1/2 =5-6d, = 4-5d, rRNA: 5 ( )
10

2. stress:
()

( ) 39



(2-
)

1) ()
( , ATG9)
2) ( )
( LC3B)
3) ( =
) ( SNAREs)
4)
40

Vellodi, A., 2005. Lysosomal storage disorders. Br. J. Haematol.


128, 413431.
Ballabio, A., Gieselmann, V., 2009. Lysosomal disorders: from
storage to cellular damage. Biochim. Biophys. Acta 1793, 684696
Schultz,M.L., Tecedor, L., Chang,M., Davidson, B.L., 2011.
Clarifying lysosomal storage diseases. Trends Neurosci. 34, 401
410
Micsenyi, M.C.,Walkley, S.U., 2012. The lysosomal system:
physiology and pathology, In: Metha, A.,Winchester, B. (Eds.),
Lysosomal Storage Disorders A Practical Guide, 1th edition
Wiley-Blackwell (John Wiley & Sons, Ltd).
Kaushik, S., Cuervo, A.M., 2012. Chaperone-mediated autophagy:
a unique way to enter the lysosome world. Trends Cell Biol. 22,
407417.
Video6

41

1)

2) Microautophagy

(
)

3)

(Chaperone-mediated
autophagy, CMA)

(one-by-one)

LAMPs

Mrschtik and Ryan, FEBS Journal 282:1858; 2015


42

- :
.
. ,
.

:

. (), , ,

,

(, , )

stress

RBCs

: 2kg . 9days 50g


( )
43

44

45

1)

( )


2)



, ,
,

:


Ganley IG. Biochemical Society Essays Biochem 55:65; 2013 46

(/) :



( )

()
()

47

, , ,

(

48

V- ( pH )
LAMPs ( )

:

6- (6)


6
TGN (pH 6,5-6,7)

TGN
(pH 6,5-6,7)
49
(1) cis-
Golgi.
(2) trans Golgi (TGN)
6-P-
(6).

TGN.
(3)
( NSF, v-SNARE, t-SNARE).
Golgi.

(4)
( 6PM ).
(5)
. .

(6)
. .

(7) /
.
.

(8)
Golgi ( ).
(9)
.
50

51


(
)


(+) .
kinesin, dynein ( )

(+) Rab7 ( GTP)

Ganley IG. Biochemical Society Essays Biochem 55:65; 2013

52

:
Rabs SNAREs

Rabs:
(60 ) GTP
(
, -
)


GEFs GTP
Ps.
Rab7: ( HOPS)

: -
Rabs

2
SNARE

53

SNAREs:


2 :
R-SNARE Q-SNAREs
(zipping-up) 2

Q-SNAREs (syntaxin 7, syntaxin 8, Vti 1b) R-SNAREs (VAMP7, VAMP8):


54
:

VAMP7

Ganley IG. Biochemical Society Essays Biochem 55:65; 2013

55

-
-

Balderhaar and Ungermann, Journal of Cell Science 126:1307; 2014 56


( )

(
)

( )
(exosomes)
(microvesicles)
xtracellular vesicles

57

1 -
(.
)

,

(. )


(.
)

58
59


Ca2+ >1

:

(
)

:
60
(, ).
:

(
)
Golgi-
(30-90%)

(V-ATP):
(),


?
(, , , ,
(??? , .
) )*
,
( )

(*)
.

.

61

( )
(TSH, insulin, Fe (transferin) ) (
)

( , )


: LDL
(22nm)

1500

800
500 -

- (
)

62
LDL
LDL (
)


pH
, LDL


LDL

,
LDL
.

63

:

( )
, ,

LDL: , -.
LDL- .
, -

HDL ( ):

64

LDL :

( ,
)

LDL

2 .

65
.

LDL

.

66

( )
(

)
( )

:
Niemann-Pick type
C1 (NPC1)

67
(T4) O

(dimeric glycoprotein, 660kDa)


thyroid follicular cells
(epithelial cells, thyrocytes)

follicular lumen

Boron WF (2003). Medical Physiology: A Cellular And


Molecular Approach. Elsevier/Saunders. p. 1300
68
(T4) O

TSH ( ) thyroid follicular cells


(epithelial cells, thyrocytes)
(colloid)
follicular lumen


T4
T4 in thyrocyte cyt
(SH)

69

( )

1) :

2)
(,
)
(
)

1)

2) ()

70

1. ( )
2.

71

72


(

)

73

(. cathepsins)

:

1)

2) (
)
Bcl-2

(.
cytochrome c and AIF)
.
(Groth-Pedersen et al., Cancer Lett 2010)

74

, ,


(, )
,


Ca2+
synaptotagmin

Saftig and Klumperman, ature Reviews, Molecular Cell Biology, 10:623; 2009
75



( )

76
-1

-

50 (, , , ,
, , sulfatases)

: (.
) Golgi
: -

: , long-lived


- (ubiquitinproteasome system, UPS)

: (proteolytic quality control)

Coutinho et al., 2015. Gene 555:50-58 77


-2
,

60 (Micsenyi and Walkley, 2012. The lysosomal system:
physiology and pathology, In: Metha, A.,Winchester, B. (Eds.), Lysosomal Storage Disorders A Practical Guide,
1th edition Wiley-Blackwell (John Wiley & Sons, Ltd)

- , ,
:
1)
2)
-

78

Coutinho et al., 2015. Gene 555:50-58

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