Evolutionary Microbiology

Chapter 10. Mitochondria –Perfectly Tamed

Jong-Soon Choi

Chungnam National Univ. GRAST

University of Science and Technology

Korea Basic Science Institute

200

Three Driving Forces

for Biological Evolution

1. DNA/RNA abiogenesis

2. Cyanobacteria occurrence

3. Mitochondria symbioant

- Self-replicating organism

from prebiotic soup

- Oxygenic photosynthesis

- Massive energy production

by respiration

(Source: www.google.com) 201

Secrets for Marathoner Maximal oxygen uptake (VO2max)

Rapid lactate clearance in muscle

Powerful Mitochondria(Source: www.google.com) 202

Mouse skeletal muscle. Bright-field

microscope. 15 μm frozen section,

Succinic DeHydrogenase stain.

Red muscle fibers (R) with a high

mitochondrial content; White muscle

fibers (W) with a low mitochondrial

content.

Flounder (광어) : white muscle

Tuna (참치) : red muscle

Fast twitch muscle (속근) Slow twich muscle (지근)

Rapid muscle contraction Slow muscle contraction

Tires quickly of fatigue Resistant to fatigue

Anaerobic exercise Aerobic exercise

Moment maximal strength available

Endurance exercise available

(Source: www.google.com) 203

Physical exercise activates PGC1

to increase [mitochondria]n

Time-course training/detraining

adaptations in mitochondrial

content of skeletal muscle.

- Disappear 50% increased

mitochondria content within 1

week

- Require 4 weeks for restoring

the 100% increased contentPGC1, Peroxisome proliferator-activated

receptor-Gamma Coactivator: a key regulator

of energy metabolism

Mitochondria

biogenesis

Energy release Lipid metabolism

(Source: www.google.com) 204

Anatomy of Mitochondria

Cellular Powerhouse

Dimension :

1~4m in length

0.5 m in width

Number : 300~400 per cell

A total of 1016 (10 times of

human microbiota)

mitochondria in human body

Function :

Control of

Energy, Sex, Suicide

(Source: www.google.com) 205

Function of Mitochondria

(1978) P. Mitschell

Mitochondrial bioenergetics

by OxPhos I to V

(1997) P Boyer & J Walker

Elucidated enzymatic

mechanism of ATP synthase

Glycolysis

Electron transfer system

Mitochondria inner

space

Mitochondria stroma

Ele

ctr

ochem

ical p

roto

n g

rad

ient

(Source: www.google.com)

206

Structure of Mitochondria

• Surface area of OM vs IM = 1:3~5

• IM : ATP synthases, cardiolipin

• Cristae : F0 particles (oxysome)

• Matrix : a total of 2/3 proteins, mtDNA

• MAM : Mitochondria-associated ER Membrane

~20% of OM, apoptosis, Ca2+ signaling

lipid biosynthesis, metabolic trafficking hub

Calcium cycling by VDAC1/IP3R and

mCU/IP3R-mNCE/SERCA(Source: www.google.com) 207

History of Mitochondria

(1886) Richard Altmann found and named ‘bioblast’

(1897) Carl Benda found mitochondria in all kinds of cells

Mitos(thread) + Chondrion(small

granule) = Mitochondria

(1912) BF Kingsbury thoughtMitochondria as respiration site

(1925) David Kellin found cytochrome

involved in respiration chain

(1941) E Kennedy & A Lehninger

found respiratory enzymes

in mitochondria(Source: www.google.com) 208

History of Mitochondria

(1918) Paul Portierthought ‘endosymbiont’

failed to find ‘proto-mitochondria’

<Les Symbiotes>

(1925) Ivan Wallin thought ‘possible new

species’ generation by

endosymiosis with mitochondria but

failed to purify ‘proto-mitochondria’

(1967) Lynn Margulis proposed Mitochondria as independent

cytoplasmic heredity site

Published in Journal of Theoretical

Biology

<The Origin of Eucaryotic Cell>

Hawaiian

Bobtailed squid

(Source: www.google.com) 209

Competition and Cooperation

Prisoner’s choice B stays silent (Cooperates) B betrays (Defects)

A stays silent (Cooperates) Each serves 1 year A : 3 years / B : goes free

A betrays (Defects) A : goes free / B : 3 years Each serves 2 years

Prisoner’s Dilemma (죄수의 딜레마) : Game Theory

• Two members of a criminal gang are arrested and imprisoned. Each prisoner is in

solitary confinement with no means of communicating with the other. The prosecutors

lack sufficient evidence to convict the pair on the principal charge. They hope to get

both sentenced to a year in prison on a lesser charge. Simultaneously, the prosecutors

offer each prisoner a bargain. Each prisoner is given the opportunity either to: betray the

other by testifying that the other committed the crime, or to cooperate with the other by

remaining silent. The offer is:

1. If A and B each betray the other, each of them serves 2 years in prison

2. If A betrays B but B remains silent, A will be set free and B will serve 3 years in prison

(and vice versa)

3. If A and B both remain silent, both of them will only serve 1 year in prison (on the

lesser charge)

What option will they choose?210

Competition and Cooperation

Suppose you're on a game show, and you're given the choice of three

doors: Behind one door is a car; behind the others, goats. You pick a

door, say No. 1, and the host, who knows what's behind the doors,

opens another door, say No. 3, which has a goat. He then says to you,

"Do you want to pick door No. 2?" Is it to your advantage to switch

your choice?

Keep No. 1?

Change No. 2?

Which choice is better?

Monty-Hall Problem – a brain teaser, the probability quiz

(Source: Wikipedia) 211

Competition and Cooperation

<Take home message>

Change of Strategy sometimes

gets better outcome

Competition < Cooperation

Monty-Hall Problem – a brain teaser, the probability quiz

Case Door 1 Door 2 Door 3 Outcome

A CAR GOAT GOAT Success

B GOAT CAR GOAT Fail

C GOAT GOAT CAR Fail

In the case of keeping Door 1

Case Door 1 Door 2 Door 3 Outcome

A CAR GOAT GOAT Fail

B GOAT CAR GOAT Success

C GOAT GOAT CAR Success

In the case of changing Door 2 or 3

P=33% Success

P=66.7% Success

(Source: Wikipedia) 212

Solar-powered Sea Slugs(바다 민달팽이)

Some sea slugs evolved a protective

mechanism to “make up” for the lack of

a protective shell. One type of sea

slug uses chloroplasts as camouflage

and energy! It feeds by slicing or

puncturing algal cells and sucking out

the cell contents. All the cell contents

are discarded except for the

chloroplasts, which are then engulfed

phagocytotically into the digestive cells.

Sea slugs blend into the green algal

bed and capture light energy to fuel

photoautotrophic carbon dioxide

fixation. These sea-slugs can

potentially live off of these carbon

products for months in the absence of

an algal food source!갯민숭달팽이

(Source: www.google.com) 213

Solar-powered Sea Slugs

Salamander is world-first photosynthetic vertebrate

Spotted salamander

embryos have an

unexpectedly close

relationship with a single-

celled alga (Source: www.google.com) 214

Evolutionary Process of Endosymbiosis

of Mitochondria

Endosymbiosis vs. Autogenesis Theory of Mitochondria

(Source: www.google.com) 215

3 COXs

3 ATPases

1 Cyt b

7 NADH-CoQRs

22 tRNAs

3 rRNAs

(Source: www.google.com)

216

Mitochondrial DNA and Diseases

Egg contains 100K to 1M mtDNA

molecules whereas a sperm contains

only 100 to 1K.

Maternal inheritance of mtDNA is

found in most animals, plants and

fungi.

Paternally inherited mitochondria

are reported in mussels and insects.

-MELAS, mitochondrial myopathy(근질환),

encephalomyopathy(뇌근육병), lactic

acidosis(젓산산증), stroke-like symptoms

-MERRF, myoclonic epilepsy(간헐성 간질)

with ragged red fibers

-MND, motor neuron disease

-Dystonia, movement disorder

Dystonia

Dystonia

(Source: www.google.com) 217

Mitochondrial Eve : Trace back through all of these natural mutations to

the origins of all modern human existence around 150KYa

Y Chromosome Adam : Passed down exclusively from father to son, date

to more than 100KYa using statistical methods (Forster et al., 2000)

(Source: www.google.com) 218

Mitochondrial Eve

(Source: www.google.com) 219

Maternal Inheritance of Mitochondrial DNA Mutations

Some mitochondrial encephalomyopathies that may be caused by mtDNA

mutations and are subject to the rules of maternal inheritance (MERRF,

MELAS, Dystonia, etc.). (Source: www.google.com) 220

Origin of Mitochondria

Rickettsia prowazekii

Nature 2002

Mitochondria share

an ancestor with

SAR11, a globally

significant marine

microbe

(Source: www.google.com) 221

Mitochondrial Uncoupling and Thermogenesis

(Left) Brown adipocytes, a in

shape, nuclei located in center, large

volume of cytoplasm and small lipid

droplets

(Right) White adipocytes, a

scant ring of cytoplasm, large lipid

droplet & flattened, eccentric nuclei(Source: www.google.com)

222

Mitochondrial Suicide

A variety of key events in apoptosis focus on

mitochondria, including the release of caspase

activators (such as cytochrome c), changes in

electron transport, loss of mitochondrial

transmembrane potential, altered cellular

oxidation-reduction, and participation of pro-

and antiapoptotic Bcl-2 family proteins.

Mitochondria and Apoptosis (Science 1998)

(Source: www.google.com) 223

Mitochondria and Aging

Mitochondrial DNA damage

and aging

ROS : superoxide anion (O2-.),

hydrogen peroxide (H2O2),

hydroxyl radicals (OH.)

(Source: www.google.com) 224