Mitochondrial Essentials

Question 1

1.

Recall which organs have the greatest energy use and demands.

Answer 1

Brain

Heart, kidney liver

Question 2

Why do mito conditions affect bain so much?

Answer 2

Brain Mitos working >5x as hard as Heart Mitos

Question 3

primary mitochondrial disease

Answer 3

genetic

exacerbated by “minor” triggers

Question 4

secondary mito disease

Answer 4

size, shape, fission/fusion, movement

in chronic ds - DM, AI, etc.

Question 5

Mito and PD

Answer 5

dec ETC action (dec ATP)
dysfunctional fission
more ROS

Question 6

MIto and AD

Answer 6

mito calcium signaling

more fission

Question 7

ALS and mito

Answer 7

mito defects

Question 8

Mfr1

Answer 8

does fusion

Question 9

DLP1

Answer 9

does fission

Question 10

mito and Breast CA

Answer 10

inc DLP1, dec Mrf2

Question 11

Sirtuin activation (IV NAD?) - promotes mito fission or fusion?

Answer 11

fusion

Question 12

•

Melatonin - promotes mito fission or fusion?

Answer 12

fusion

Question 13

•

Betaine - promotes mito fission or fusion?

Answer 13

fusion

Question 14

Palmitate- promotes mito fission or fusion?

Answer 14

fission

Question 15

indomethacin- promotes mito fission or fusion?

Answer 15

fission

Question 16

S/Sx suggesting mitochondropathy

Answer 16

ptosis
ophthamoplegia
fatigue
diabetes
"hypoglycemia

Question 17

S/Sx suggesting mitochondropathy

Answer 17

ptosis
ophthamoplegia
deafness
fatigue
diabetes
"hypoglycemia"
protein wasting
cardiomyopathy
cardiac conduction defects
WPW
tachycardia
liver failure

depression
migraines
headaches
weakness
dysautonomia
fainting
neuropathic pain 
constipation/diarrhea
pseudo-obstruction
GERD
muscle wasting
exocrine pancreatic failure (can't make pancreatic enzymes)

Question 18

CoQ10 level and effect

Answer 18

> 1.7 (or 2)

dec cardiac mortality

Question 19

Carnitine indications

Answer 19

DM
sepsis
cardiomyopathy
renal ds?

Question 20

“liver enzymes” and mito/oxid stress

Answer 20

AST and ALT increased to help replete GSH (needs aspartate and alanine)

Question 21

SAM-e and mito

Answer 21

methylation is dependent on mitochondria! needs ATP

Question 22

SAM-e and liver cirrhosis

Answer 22

treat early and long-term - decreases liver transplant

Question 23

SAM-e and NASH

Answer 23

low SAMe leads to low mito GSH –> NASH

Question 24

what can be used in depression, OA, and HCV?

Answer 24

SAMe

Question 25

Silymarin = ? and effect and specific application

Answer 25

= milk thistle protects mitochondria! helps with chronic liver ds

Question 26

vit D and mito

Answer 26

helps with better mitochondrial function | improves

Question 27

Conditions that are examples of intracellular energy deficits.

Answer 27

obesity, CHF, cachexia, diabetes, fatty liver

Question 28

PGC1-alpha

Answer 28

induces mitochondrial biogenesis

Question 29

how to make more brown fat? inducing... lifestyle supp/phyto

Answer 29

AMPK cold polyphenols ALA

Question 30

ALA (alpha lipoic acid) actions

Answer 30

makes more brown fat via AMPK increases glutathione/anti-ox metal chelator

Question 31

ALA effect on met syn

Answer 31

helps with glucose/lipid metabolism, PCOS, TGs

Question 32

ALA dose and caveat

Answer 32

60 to 2400 mg in divided doses | *extended release to avoid hypoglycemia with higher doses

Question 33

Low WBC, Neutrophils, and Platelets in mito w/u

Answer 33

•Seen in High Ox Stress States

Question 34

GGT in mito lab w/u:

Answer 34

Marker of GSH recycling, oxidative stress exposures, | POP accumulation, DMII risk

Question 35

Mag and mito

Answer 35

needed to activate ATP! | can cause aching, neuro Sx

Question 36

Ammonia in mito lab w/u

Answer 36

if high, indicates high MTP activity - sign of mito dysfunction and oxid stress **ARGININE!***

Question 37

L:P ratio in mito w/u | and how to check!

Answer 37

if high, think ETC deficit (or false pos in acute illness) | First Morning Elevated Urine Lactate

Question 38

plasma AA and mito lab w/u

Answer 38

if global elevation --> catabolism | esp alanine!

Question 39

acyl-carnitine and mito lab w/u

Answer 39

use in ASD to check for inherited mito ds

Question 40

CoQ10 uses

Answer 40

``` hypertension CHF hld depression fatigue athletic performance/recovery Neurodeg AD, PD, HD ```

Question 41

CoQ10 uses

Answer 41

``` hypertension CHF HLD fatigue athletes neurodegeneration AD, PD, HD ```

Question 42

Oxidative Stress Markers

Answer 42

DNA - 8OHdg fats - lipid perox, oxLDL, isoprostane-F2 carb - HbA1C, AGEs protein- 3 Nitrotyrosine Others - Total Antioxidant Capacity (TAC) - Micronutrient Deficiency serum, RBC, urine

Question 43

Oxidative Stress Markers in mito lab w/u

Answer 43

DNA - 8OHdg fats - lipid perox, oxLDL, isoprostane-F2 carb - HbA1C, AGEs protein- 3 Nitrotyrosine Others - Total Antioxidant Capacity (TAC) - Micronutrient Deficiency serum, RBC, urine

Question 44

ETC & Citrate Synthase Activity in mito lab w/u

Answer 44

done by muscle biopsy (or buccal swab - experimental)

Question 45

TRAP1 Gene SNPs

Answer 45

``` hurt, tired, and queasy chronic pain, fatigue, GI dysmotility "Susan" 1-2% of population in European derived Tx: aggressive anti-oxid ```

Question 46

Metabolic Tx for mito diseases

Answer 46

``` Primary: B vitamins (B1, B2, B3, B5, B6, B12, Folate, Biotin) Iron, Mag CoQ10 Carnitine ``` Secondary: Creatine - source of high energy phosphate, buffers ATP, increased exercise/strength but not body comp AA rebalancing SAMe

Question 47

Lipid support Tx for mito ds

Answer 47

Oral: If fecal fat, GI symptoms, dry skin, consider supporting Pancreatic Lipase, Bile Acids Phosphatidyl Choline (PC) - lipid that is part of mito membrane Fish oil (EPA/DHA) Flax Oil (aLA) Evening Primrose Oil/Borage oil (GLA) Secondary: IV Lipid Replacement

Question 48

Oxidative Stress Tx for mito ds

Answer 48

Direct: Direct Anti oxidants: Vitamin C, Vitamin A, Vitamin E ALA, CoQ10 NAC (critical factor for GSH) Se, Cu, Mn (cofactors for antioxidant enzymes) ``` Indirect sulforaphane resveratrol curcumin EGCG blueberries ```

Question 49

Detox & Inflamm Reduction Interventions for mito ds.

Answer 49

Detox Enzymes etc - sulforaphane, glucosinolate, quercetin - silymarin (milk thistle) - NAC - TMG choline - SAM2 Direct glutathione (various methods)

Question 50

What is Phosphatidyl Choline (PC)

Answer 50

lipid that is part of mito membrane