Mitochondria

ATP-­‐  “the  free-­‐energy  currency”

– Every  day,  we  build  bones,  

move  muscles,  think,  and  
perform  many  other  ac=vi=es  
with  our  bodies.  All  of  these  
ac=vi=es  are  based  upon  
energy  .              
?
– ATP:  The  Perfect  Energy  
Currency  for  the  Cell
                                                   
 Mitochondria-­‐  
 the  power  plants  of  ATP
• Mitochondria  are  double  layer  membrane-­‐enclosed  
organelles  distributed  through  the  cytosol  of  most  
eukaryo=c  cells.  Their  main  func=on  is  the  conversion  of  
the  poten=al  energy  of  food  molecules  into  ATP.  So  
mitochondria  are  also  called  “the  powerhouse”  of  the  cell.    
• In  addi=on  to  supplying  cellular  energy,  mitochondria  are  
involved  in  cell  death,  as  well  as  the  control  of  the  cell  cycle  
and  cell  growth.  
 Brief History of Mitochondria studies
• Kalliker-­‐  told  first  =me  about  mitochondria  
• Richard  Altman  1894,  established  them  as  cell  organelles  and  called  
them  "bioblasts".  
• The  term  "mitochondria"    was  coined  by  Carl  Benda  in  1898.  
• Leonor  Michaelis  discovered  Janus  green  can  be  used  as  a  supravital  
stain  for  mitochondria  in  1900.    
• In  1913  par=cles  from  extracts  of  guinea-­‐pig  liver  were  linked  to  
respira=on  by  OBo  Heinrich  Warburg,  which  he  called  "grana".    
• The  first  high  resolu=on  micrographs  appeared  in  1952,  replacing  the  
Janus  Green  stains  .  
• The  popular  term  "powerhouse  of  the  cell"  was  coined  by  Philip  
Siekevitz  in  1957.  
• Plant  cells-­‐  F.  Meves
Mitochondrial Morphology and Structure

I. Shape, size & number

• Mitochondria   are   oRen   flexible,   rod-­‐shaped   organelles   that   are  
about   0.5   to   1μm   in   girth   and   as   much   as   7   μ   m   in   length.  
Mitochondria  vary  considerably  in  size  &  shape.    
• Their  number  correlate  with  the  metabolic  ac=vi=es  of  the  cell.  
 II Ultrostructure and
Functional Localization

• 1.  Outer  membrane    
• 2.  Inner  membrane    
• 3.  Inter  membrane  space  
• 4.  TranslocaSon  contact  site        
•  5.Matrix  
•  6.  Cristae  
 II Ultrostructure and
Functional Localization
 II Ultrostructure and
Functional Localization
• 1. Outer  membrane  
•  contains  many  complexes  of  integral  membrane  proteins  
that  form  channels  through  which  a  variety  of  molecules  
and  ions  move  in  and  out  of  the  mitochondrion.  we  called  
it   porins.   These   porins   form   channels   that   allow  
molecules   5000   Daltons   or   less   in   molecular   weight   to  
freely   diffuse   from   one   side   of   the   membrane   to   the  
other.  
2. Inner  membrane  
• The  inner  membrane,  which  encloses  the  matrix  space,  is  
folded  to  form  cristae.  The  area  of  the  inner  membrane  
is  about  five  =mes  as  great  as  the  outer  membrane.    
• This   membrane   is   richly   endowed   with   cardiolipin,   a  
phospholipid   that   possesses   four,   rather   than   the   usual  
two,  faZy  acyl  chains.  The  presence  of  this  phospholipid  
in  high  concentra=on  makes  the  inner  membrane  nearly  
impermeable  to  ions,  electrons,  and  protons.  
• The  inner  membrane  has  a  very  high  protein-­‐to-­‐
phospholipid  ra=o  (about  4:1  by  weight).
• Impermeable to most charged molecules
Inner   membrane   contains   three   major   types  
of  proteins:  
• ① those   that   carry   out   the   oxida=on      
 reac=ons  of  the  respiratory  chain  
• NADH  dehydrogenase  
• Cytochrome  b-­‐c1  
• Cytochrome  oxidase  
• ②  ATP  synthetase    
• ③ specific  transport  proteins
• 3. Inter  membrane  space  
• contains  several  enzymes  that  use  the  ATP  that  passes  out  of  
the  matrix  to  phosphorylate  other  nucleo=des.  
• 4.  TranslocaSon  contact  site  
• TOM(Translocon  of  the  outer  membrane)  
• TIM(Translocon  of  the  inner  membrane)  
• 5. Matrix  
•   contains   hundreds   of   different   enzymes   including  
those  required  for  
• ①the  oxida=on  of  pyruvate  and  faZy  acids  
• ②the  citric  acid  cycle.  
• It  also  contains  small  amounts  of  mitochordrial  DNA  
genome,   special   mitochondrial   ribosomes,   tRNAs  
and   various   enzymes   that   required   for   the  
expression  of  the  mitochondrial  genes.    
 Chemical  composiSon:    
• The  outer  membrane  consists  of  40%  lipids  and  60  percent  
proteins.      
• The  inner  membrane  is  made  up  of  20%  lipids  and  80%  
proteins.    The  electron  transport  enzymes,  proton  secre=ng  
proteins  are  virtually  buried  in  the  core  of  the  inner  
membranes.  
•  Mitochondrial  matrix  also  consists  of  a  wide  variety  of  
enzymes.  There  are  more  than  120  kinds  of  enzymes  of  
mitochondrial.    
• Mitochondrial  matrix  also  contains  DNA,  RNA  molecules.  
The  mitochondrial  genome  
• The   human   mitochondrion   contains   5-­‐10   iden=cal   molecules  
of   DNA.   Mitochondrial   DNA(mtDNA)   are   circular,   double-­‐
stranded   structures   of   molecules   in   higher   eukaryotes.   They  
encode  their  own  mRNA,  rRNA  and  ribosomal  proteins,  tRNAs  
and  a  few  mitochondrial  proteins.    
• Each  mitochondrion  consists  of  16’569  base  pairs  carrying  the  
informa=on  for  37  genes.
• but  only  13  of  these  code  for  polypep=des,  the  remainder  
being  the  2  ribosomal  subunits  and  22  types  of  transfer  RNA.    
• However, most of the proteins in the mitochondrion are
encoded in nucleus by nuclear DNA, synthesized in cytosol,
and subsequently transported into the mitochondrion.
• Because  the  growth  and  prolifera=on  of  
mitochondria  are  controlled  by  both  nuclear  
genome  and  it’s  own  genome.  Mitochondria  
are  usually  called  semiautonomous  organelle.  
 The  transport  protein  into  
Mitochondria  

• Mitochondrial  proteins  are  first  fully  synthesized  

as  precursor  proteins  in  the  cytosol  and  then  
translocated  into  mitochondria  by  a  
pos$ransla)onal  mechanism.  
1.  TranslocaSon  into  the  Mitochondrial  Matrix  Depends  on  a  
Signal  Sequence  and  Protein  Translocators  
 2.  Mitochondrial  Precursor  Proteins  Are  Imported  as  
Unfolded  PolypepSde  Chains.

• Mitochondrial  precursor  proteins  do  not  fold  into  their  na=ve  

structures  aRer  they  are  synthesized;  instead,  they  remain  
unfolded  through  interac=ons  with  other  proteins  in  the  
cytosol(hsp70).  
N-terminal signal sequence is recognized by receptors of TOM;
The protein is translocated across both Mit membranes at or near
special contact sites.
ATP Hydrolysis and a H+ Gradient are Used to Drive
Protein Import into Mitochondria.
Proper folding ensure the maturation of Mitochondria
proteins.

After the initial interaction with mitochondrial hsp70, many imported

proteins are passed on to another chaperone protein, mitochondrial
hsp60 that facilitates its folding by binding and releasing it through
cycles of ATP hydrolysis.
Protein Transport into the Inner Mitochondrial Membrane
and the Intermembrane Space Requires Two Signal
Sequences
Origin  and  replicaSon  of  mitochondria  

• Origin  of  mitochondria  

• Many of the features of the mitochondrial genetic
system resemble those found in prokaryotes like
bacteria. This has strengthened the theory that
mitochondria are the evolutionary descendants of a
prokaryote that established an endo-symbiotic
relationship with the ancestors of eukaryotic cells
early in the history of life on earth.
 Mitochondria  replica=on
• Mitochondria  replica=on  much  like  bacterial  
cells.  When  they  get  too  large,  they  undergo  
fission.  This  involves  a  furrowing  of  the  inner  
and  then  the  outer  membrane  as  if  someone  
was  pinching  the  mitochondrion.  Then  the  
two  daughter  mitochondria  split.    
 II Cellular respiration and Energy
Conversion
• 1.  Cellular  respiraSon  
• Cellular  respira=on  is  the  process  of  oxidizing  food  
molecules  to  carbon  dioxide  and  water.  The  energy  
released    is  trapped  in  the  form  of  ATP  for  use  by  all  
the  energy-­‐consuming  ac=vi=es  of  the  cell.    
• The  process  occurs  in  two  phases:    
Glycolysis:  the  breakdown  of  glucose  to  pyruvic  acid    
oxidaSon  of  pyruvic  acid  to  carbon  dioxide  and  
water