Table 2.

A summary of biochemical assays conducted on peripheral tissues from PD patients. The different peripheral tissues assayed are (A) platelets, (B) lymphocytes, (C) skeletal muscle, and (D) skin fibroblasts. C: control; SC: spousal control to account for environmental conditions; PD: Parkinson’s disease; PDS: sporadic PD; PDF: patients with first degree relatives with PD; DA: dopaminergic; N.D.: not described; N.S.: no statistically significant difference between PD and control subjects; CI: NADH: CoQ₁ oxidoreductase activity; CI + III: NADH: cytochrome c oxidoreductase activity; CII + III: succinate: cytochrome c oxidoreductase activity; CIV: cytochrome c oxidase activity; CS: citrate synthase activity; The color “blue” denotes that the activities were determined with a complex-specific inhibitor (rotenone for CI, antimycin A for CIII); “x/CS” refers to activity x (CI, CII, CIII, or CIV) normalized to citrate synthase activity. L-dopa: Levodopa; OCR: oxygen consumption rate; [³H] DHR: [³H]dihydrorotenone; The symbol (#) denotes that there was no correlation between activity levels and age at onset of disease, severity of disease, duration of disease, and/or treatment. The studies are grouped based on the presence (light green cells) vs absence (light red cells) of significant difference in CI between control and PD.

Table 2A. Assessment of ETC function in platelets
Study	Source	No. of cases	Medications for PD	Results
Parker et al., 1989	Mitochondria (Percoll gradient)	8 C, 10 PD	8 on L-dopa and other drugs; 2 untreated	~54% decrease in CI activity. N.S. for CII+III and CIV.
Krige et al., 1992	Mitochondria (differential centrifugation)	15 C, 25 PD	21 on L-dopa; 4 untreated	~16% decrease in CI/CS activity; N.S. for CII+III, CIV, and CS; (#)
Yoshino et al., 1992	Homogenates	17 C, 20 PD	17 on L-dopa; 12 on trihexyphendyl; 6 on bromocriptine	~26% decrease in CI activity; ~19% decrease in CII; N.S. for CIII and CIV; (#)
Benecke et al., 1993	Mitochondria (sucrose gradient ultracentrifugation)	44 C, 27 PD	24 on L-dopa/Carbidopa, selegeline/bromocriptine, cabergoline or lisuride; 3 untreated	~51% statistically significant decrease in piericidinA - sensitive CI activity; ~30% decrease in CIV. N.S. for CIII. 5 early-stage PD measured after one year: CI and CIV activities decreased after one year. N.S. for patients >3 years after diagnosis; (#)
Haas et al., 1995	Mitochondrial (Percoll gradient ultracentrifugation); No medications for at least one month before testing	18 C, 13 SC, 18 PD	1 on trihexylphenidyl; 1 on amantadine; 2 on L-dopa/Carbidopa; 5 on selegiline; Some subjects also received other drugs	~23% decrease in PD CI/CS, ~20% decrease in CII+III/CS. N.S. for CIV and CS. No correlation between activities and medications.
		13C, 13 SC, 13 PD		Compared to age/sex-matched controls (C):~ 32% decrease in CI and ~28% decrease in CII+III activities; N.S. for CI/CS, CII+III/CS and CIV/CS. Compared to SC: ~29% decrease in CI activity, N.S. for CI/CS, CII+III, CIV.
Gu et al., 1998	Mitochondira (differential centrifugation)	8 C, 8 PD	All receiving L-dopa	~24% decrease in CI/CS; N.S. for CII+III/CS and CIV/CS. 4 PD with worst CI activities chosen to be studied over time: after 1 and 2 months, CI/CS retained similar deficiency.
Varghese et al., 2009	Homogenates	30 C, 10 PD	1 under dopamine replacement therapy; others, N.D.	~50% decrease in NADH: CoQ0 oxidoreductase activity assessed without testing for rotenone sensitivity; N.S. for CII; CIII, CIV: N.D.
Bravi et al., 1992	Mitochondria (differential centrifugation); Medications stopped for minimum 8 h before obtaining platelets	13 C, 17 PD	8 on L-dopa/Carbidopa (4 with selegeline), 2 on selegeline (with lisuride or amantadine), 7 untreated.	N.S for CI, CII+IIII, CIV activities, and CI-linked OCR; (#)
Mann et al., 1992a	Platelet homogenates	15 C, 14 PD	12 on L-dopa.	N.S. for CI, CII+III, CIV activities, before and after CS normalization.
Taylor et al., 1994	Mitochondria (differential centrifugation)	15 C, 7 PD	All on selegeline and L-dopa;	N.S. for CI, CII+III, CIV activities; (#)
Shults et al., 1995	Mitochondira (differential centrifugation)	11 PD, 0 C	Three measures: Before medication, 1 month after Carbidopa/L-dopa, and 1 month after Carbiopa/L-dopa + selegiline.	N.S. for CI, CII+III, CIV, and CS activities before or after medications.
Blake et al., 1997	Mitochondria (Percoll gradient centrifugation)	9 C, 13 PD	2 untreated; 11 on Carbidopa/L-dopa, with or without selegiline, with or without dopamine agonist or anticholinergic medication - 5 had discontinued drugs 10 days before study.	N.S, for CI, CIII, CIV activities before and after CS normalization; (#)
Blandini et al., 1998	Washed platelets	16 SC, 16 PD	All receiving L-dopa.	Platelet [3H]DHR binding assay: N.S. for specific binding of [3H]DHR; N.S. for percentage of [3H]DHR binding inhibition by 1 mM MPP+; a correlation was found in % MPP+ inhibition of DHR specific binding and L-dopa dosage; (#)
Hanagasi et al., 2009	Mitochondria (differential centrifugation)	17C, 17 PDF, 15 PDS	All receiving L-dopa and/or DA drug treatment.	N.S. for CI, CII+III, CIV, before and after CS normalization; (#)
Bronstein et al., 2015	Mitochondria (Percoll gradient ultracentrifugation); No medications at least 12 h before testing	23 C, 23 PD	N.D.	N.S. for CI and CI+III activities, before and after CS normalization; CIVN.D.; No correlation between CI/CS activity and pesticide exposure. Inverse correlation for CI inhibitors and dithiocarbamates with CI+III activity.
Table 2B. Assessment of complex I function in lymphocytes
Study	Source	No. of cases	Medications for PD	Results
Barroso et al., 1993	Homogenates	15 C, 16 PD	Not treated	~25% decrease CI+III; ~45% decrease in CIV; N.S. for CII+III activity.
Shinde et al., 2006	Homogenates	30 C, 40 PD	All on L-dopa	~12% decrease in CI+III, ~26% decrease in CIV, N.S. for CII CII+III, CS activities.
Müftüoglu et al., 2003	Leukocyte mitochondria	17 C, 10 Parkin PD, 20 iPD	All on L-dopa, selegiline, and/or pergolide.	~ 62% and ~64% decrease in CI in Parkin PD and iPD, respectively; ~ 60% decrease in CIV activity for iPD, N.S. for CIV activity in Parkin PD; (#)
Yoshino et al., 1992	Homogenates	17 C, 20 PD	17 on L-dopa; 12 on trihexyphendyl; 6 on bromocriptine.	N.S. for CI, CIII, and CIV activities; ~13.2% decrease in CII activity; (#)
Martin et al., 1996	Mitochondria (differential centrifugation)	30 C and 36 PD; ~2.6 years of PD duration	Not treated	N.S. for CI, CI+III, CII, CII+III, CIV, normalized to protein content or CS activity; (#)
Ming et al., 2020	Immortalized lymphocyte mitochondria	3 C, 3 PDS, 3 Parkin PD	N.D.	N.S. for immunocaptured CI activity
Table 2C. Assessment of complex I function in skeletal muscle
Study	Source	No. of cases	Medications for PD	Results
Bindoff et al., 1989; Bindoff et al., 1991	Vastus lateralis mitochondria	7 C, 5 PD	1 untreated; 1 on sinemet; 1 on sinemet, orphenadrine; 1 on madopar, bromocriptine, diazepam; 1 on sinemet, benzhexol, triazolam.	In 5 C, 4 PD; ~40% decrease in CI activity, ~49% CII activity; ~40% decrease in CIV activity; CIII N.D; In 7 C, 5 PD: CI-linked respiration decreased.
				SDS-PAGE immunoblot using antibody against CI holoenzyme: 2 out of 3 patients show decreased accumulation of subunits
Nakagawa-Hattori et al., 1992	ilipsoas or quadriceps mitochondria.	6 C, 4 PD	N.D.	~48% decrease in CI activity. N.S. for CII, CIII, CIV activities
Shoffner et al., 1992	Quadriceps mitochondria	16 C, 6 PD	All received L-dopa/Carbidopa + combinations of other medications.	5 out of 6 PD had decreased CI and CI+III activities; One patient had CI, CII+III, CIV deficiency; one patient had decreased activities for CI, CII, CI+III; one patient had decreased CI and CII+III. An association between the severity of CI defect and the level of disability stages observed. No correlation of CI activity with age observed.
Cardellach et al., 1993	Left vastus lateralis mitochondria	10 C, 8 PD	6 on L-dopa/Carbidopa; 1 on selegiline; 1 on amantadine.	~ 25% decrease in CI activity; ~68% decrease in CIV activity; N.S. for CII, CIII, CV activites, and CI-linked OCR; (#)
Blin et al., 1994	Biceps brachii or deltoid muscle mitochondria	43 C, 27 PD	6 untreated; 21 on L-dopa.	CI activity: ~71% decrease in treated patients, ~67% decrease in untreated patients. ~34% decrease in CIII activity for only treated patients; N.S. for CII and CIV; (#)
Wiedemann et al., 1999	Mitochondria from saponin-permeabilized M.vastus lateralis fibers	32 C, 15 PD	N.D.	~30% decrease in CI+III/CS; N.S. for CII+III/CS, CIV/CS; ~50% increase in CS activity; Flux control coefficient of CI and CIV increased. N.S. for CI-linked respiration.
Winkler-Stuck et al., 2005	Homogenates	36 C, 19 PD	15 PD on L-dopa	~33% and ~30% decrease in CI/CS and CI+III/CS activities, respectively; ~30% decrease for CIV/CS; N.S. for CII+III/CS; Increased CI and CIV flux control coefficients. No decrease in CI-linked respiration.
Mann et al., 1992a	Left vastus lateralis mitochondria	6 C, 9 PD	5 untreated; 4 on L-dopa.	N.S. for CI, CII+III, CIV activities. N.S. for CI-linked OCR (6 C, 9 PD); No difference in activities in treated vs untreated PD.
Anderson et al., 1993	Quadriceps mitochondria	6 C, 7 PD	6 on L-dopa or Carbidopa and other drugs; 1 untreated.	N.S. for CI+III, CII+III or CIV activities, and CI-linked OCR; (#)
DiDonato et al., 1993	Left quadriceps homogenates and mitochondria	6C, 6 PD (mitochondria), 8 C, 16 PD (homogenates)	2 untreated; rest on L-dopa.	N.S. for CI, CII, CII+III, or CIV activities in muscle homogenates and mitochondria; (#)
Manneschi et al., 1994	Left quadriceps mitochondria	53 C, 6 PD out of which 2 PDF	N.D.	N.S for CI/CS, CII+III/CS, CIV/CS activities.
Taylor et al., 1994	Left vastus lateralis mitochondria	6 C, 3 PD	2 untreated; 1 on selegeline and L-dopa.	N.S. for CI, CII+III, CIV activities; N.S. for CI-linked OCR (5 C, 3 PD).
Table 2D. Assessment of complex I function in skin fibroblasts
Study	Source	No. of cases	Medications for PD	Results
Wiedemann et al., 1999	Digitonin-permeabilized skin fibroblasts	14 C, 14 PD	N.D.	N.S for CI-linked OCR. Increased CI and CIV flux control coefficient. Enzymatic activities N.D.
Ambrosi et al., 2014	Cultured fibroblasts	7 C, 11 PDS	N.D.	Maximal respiration and rotenone-sensitive respiration were decreased. Enzymatic activities N.D.
Winkler-Stuck et al., 2004	Cultured fibroblasts	13 C, 18 PD	15 PD on L-dopa	Increased CI and CIV flux control coefficient; N.S. for CII+III/CS and CIV/CS activity; CI/CS increased by ~ 54%. N.S. for OCR.
Carling et al., 2020	Cultured fibroblasts	50 C, 100 PDS	N.D.	N.S. for ATP levels, mitochondrial membrane potential; (#)
		5 C, 5 PDS		5 PDS patients selected for most severe ATP defect: Decreased NDUFB8 (CI subunit) and COX2 (CIV subunit) determined by SDS-PAGE immunoblot.
		6 C, 6 PDS		75% decrease in immunocaptured CI activity; 37% decrease in CIV activity.
del Hoyo et al., 2010	Cultured fibroblasts	19 C, 20 PD	18 PD treated with L-dopa, dopamine agonists, selegiline, rasagiline, anticholinergics, and/or amantadine.	N.S. for CI, CII, CIII, CIV, CI+III, CII+III activities normalized to either protein amount or CS activity; ~20% decrease in CV activity normalized to protein or CS activity;